Mechanics of Sister Chromatids studied with a Polymer Model English</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p>
<p>Zhang, Yang; Isbaner, Sebastian; Heermann, Dieter</p>
<p>2013-10-01</p>
<p>Sister chromatid cohesion denotes the phenomenon that sister chromatids are initially attached to each other in mitosis to guarantee the error-free distribution into the daughter cells. Cohesion is mediated by binding proteins and only resolved after mitotic chromosome condensation is completed. However, the amount of attachement points required to maintain sister chromatid cohesion while still allowing proper chromosome condensation is not known yet. Additionally the impact of cohesion on the mechanical properties of chromosomes also poses an interesting problem. In this work we study the conformational and mechanical properties of sister chromatids by means of computer simulations. We model both protein-mediated cohesion between sister chromatids and chromosome condensation with a dynamic binding mechanisms. We show in a phase diagram that only specific link concentrations lead to connected and fully condensed chromatids that do not intermingle with each other nor separate due to entropic forces. Furthermore we show that dynamic bonding between chromatids decrease the Young's modulus compared to non-bonded chromatids.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1205336','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1205336"><span>Replication-Dependent Sister Chromatid Recombination in Rad1 Mutants of Saccharomyces Cerevisiae</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Kadyk, L. C.; Hartwell, L. H.</p>
<p>1993-01-01</p>
<p>Homolog recombination and unequal sister chromatid recombination were monitored in rad1-1/rad1-1 diploid yeast cells deficient for excision repair, and in control cells, RAD1/rad1-1, after exposure to UV irradiation. In a rad1-1/rad1-1 diploid, UV irradiation stimulated much more sister chromatid recombination relative to homolog recombination when cells were irradiated in the G(1) or the G(2) phases of the cell cycle than was observed in RAD1/rad1-1 cells. Since sister chromatids are not present during G(1), this result suggested that unexcised lesions can stimulate sister chromatid recombination events during or subsequent to DNA replication. The results of mating rescue experiments suggest that unexcised UV dimers do not stimulate sister chromatid recombination during the G(2) phase, but only when they are present during DNA replication. We propose that there are two types of sister chromatid recombination in yeast. In the first type, unexcised UV dimers and other bulky lesions induce sister chromatid recombination during DNA replication as a mechanism to bypass lesions obstructing the passage of DNA polymerase, and this type is analogous to the type of sister chromatid exchange commonly observed cytologically in mammalian cells. In the second type, strand scissions created by X-irradiation or the excision of damaged bases create recombinogenic sites that result in sister chromatid recombination directly in G(2). Further support for the existence of two types of sister chromatid recombination is the fact that events induced in rad1-1/rad1-1 were due almost entirely to gene conversion, whereas those in RAD1/rad1-1 cells were due to a mixture of gene conversion and reciprocal recombination. PMID:8454200</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('http://hdl.handle.net/2060/20150003185','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/20150003185"><span>Detection of Chromosomal Inversions Using Non-Repetitive Nucleic Acid Probes</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p>
<p>Ray, F. Andrew (Inventor); Goodwin, Edwin H. (Inventor); Bedford, Joel S. (Inventor); Cornforth, Michael N. (Inventor); Bailey, Susan M. (Inventor)</p>
<p>2014-01-01</p>
<p>A method and a kit for the identification of chromosomal inversions are described. Single-stranded sister chromatids are generated, for example by CO-FISH. A plurality of non-repetitive, labeled probes of relatively small size are hybridized to portions of only one of a pair of single-stranded sister chromatids. If no inversion exists, all of the probes will hybridize to a first chromatid. If an inversion has occurred, these marker probes will be detected on the sister chromatid at the same location as the inversion on the first chromatid.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('http://hdl.handle.net/2060/20120016379','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/20120016379"><span>Detection of chromosomal inversions using non-repetitive nucleic acid probes</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p>
<p>Bedford, Joel S. (Inventor); Cornforth, Michael N. (Inventor); Bailey, Susan M. (Inventor); Ray, F. Andrew (Inventor); Goodwin, Edwin H. (Inventor)</p>
<p>2012-01-01</p>
<p>A method for the identification of chromosomal inversions is described. Single-stranded sister chromatids are generated, for example by CO-FISH. A plurality of non-repetitive, labeled probes of relatively small size are hybridized to portions of only one of a pair of single-stranded sister chromatids. If no inversion exists, all of the probes will hybridize to a first chromatid. If an inversion has occurred, these marker probes will be detected on the sister chromatid at the same location as the inversion on the first chromatid.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17630407','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17630407"><span>A comparison of G2 phase radiation-induced chromatid break kinetics using calyculin-PCC with those obtained using colcemid block.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Bryant, Peter E; Mozdarani, Hossein</p>
<p>2007-09-01</p>
<p>To study the possible influence of cell-cycle delay on cells reaching mitosis during conventional radiation-induced chromatid break experiments using colcemid as a blocking agent, we have compared the chromatid break kinetics following a single dose of gamma rays (0.75 Gy) in metaphase CHO cells using calyculin-induced premature chromosome condensation (PCC), with those using colcemid block. Calyculin-induced PCC causes very rapid condensation of G2 cell chromosomes without the need for a cell to progress to mitosis, hence eliminating any effect of cell-cycle checkpoint on chromatid break frequency. We found that the kinetics of the exponential first-order decrease in chromatid breaks with time after irradiation was similar (not significantly different) between the two methods of chromosome condensation. However, use of the calyculin-PCC technique resulted in a slightly increased rate of disappearance of chromatid breaks and thus higher frequencies of breaks at 1.5 and 2.5 h following irradiation. We also report on the effect of the nucleoside analogue ara A on chromatid break kinetics using the two chromosome condensation techniques. Ara A treatment of cells abrogated the decrease in chromatid breaks with time, both using the calyculin-PCC and colcemid methods. We conclude that cell-cycle delay may be a factor determining the absolute frequency of chromatid breaks at various times following irradiation of cells in G2 phase but that the first-order disappearance of chromatid breaks with time and its abrogation by ara A are not significantly influenced by the G2 checkpoint.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2567865','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2567865"><span>Shugoshin1 May Play Important Roles in Separation of Homologous Chromosomes and Sister Chromatids during Mouse Oocyte Meiosis</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Yin, Shen; Ai, Jun-Shu; Shi, Li-Hong; Wei, Liang; Yuan, Ju; Ouyang, Ying-Chun; Hou, Yi; Chen, Da-Yuan; Schatten, Heide; Sun, Qing-Yuan</p>
<p>2008-01-01</p>
<p>Background Homologous chromosomes separate in meiosis I and sister chromatids separate in meiosis II, generating haploid gametes. To address the question why sister chromatids do not separate in meiosis I, we explored the roles of Shogoshin1 (Sgo1) in chromosome separation during oocyte meiosis. Methodology/Principal Findings Sgo1 function was evaluated by exogenous overexpression to enhance its roles and RNAi to suppress its roles during two meioses of mouse oocytes. Immunocytochemistry and chromosome spread were used to evaluate phenotypes. The exogenous Sgo1 overexpression kept homologous chromosomes and sister chromatids not to separate in meiosis I and meiosis II, respectively, while the Sgo1 RNAi promoted premature separation of sister chromatids. Conclusions Our results reveal that prevention of premature separation of sister chromatids in meiosis I requires the retention of centromeric Sgo1, while normal separation of sister chromatids in meiosis II requires loss of centromeric Sgo1. PMID:18949044</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3514784','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3514784"><span>Cell elongation is an adaptive response for clearing long chromatid arms from the cleavage plane</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Kotadia, Shaila; Montembault, Emilie; Sullivan, William</p>
<p>2012-01-01</p>
<p>Chromosome segregation must be coordinated with cell cleavage to ensure correct transmission of the genome to daughter cells. Here we identify a novel mechanism by which Drosophila melanogaster neuronal stem cells coordinate sister chromatid segregation with cleavage furrow ingression. Cells adapted to a dramatic increase in chromatid arm length by transiently elongating during anaphase/telophase. The degree of cell elongation correlated with the length of the trailing chromatid arms and was concomitant with a slight increase in spindle length and an enlargement of the zone of cortical myosin distribution. Rho guanine-nucleotide exchange factor (Pebble)–depleted cells failed to elongate during segregation of long chromatids. As a result, Pebble-depleted adult flies exhibited morphological defects likely caused by cell death during development. These studies reveal a novel pathway linking trailing chromatid arms and cortical myosin that ensures the clearance of chromatids from the cleavage plane at the appropriate time during cytokinesis, thus preserving genome integrity. PMID:23185030</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/15162016','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/15162016"><span>Progress towards understanding the nature of chromatid breakage.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Bryant, P E; Gray, L J; Peresse, N</p>
<p>2004-01-01</p>
<p>The wide range of sensitivities of stimulated T-cells from different individuals to radiation-induced chromatid breakage indicates the involvement of several low penetrance genes that appear to link elevated chromatid breakage to cancer susceptibility. The mechanisms of chromatid breakage are not yet fully understood. However, evidence is accumulating that suggests chromatid breaks are not simply expanded DNA double-strand breaks (DSB). Three models of chromatid breakage are considered. The classical breakage-first and the Revell "exchange" models do not accord with current evidence. Therefore a derivative of Revell's model has been proposed whereby both spontaneous and radiation-induced chromatid breaks result from DSB signaling and rearrangement processes from within large looped chromatin domains. Examples of such rearrangements can be observed by harlequin staining whereby an exchange of strands occurs immediately adjacent to the break site. However, these interchromatid rearrangements comprise less than 20% of the total breaks. The rest are thought to result from intrachromatid rearrangements, including a very small proportion involving complete excision of a looped domain. Work is in progress with the aim of revealing these rearrangements, which may involve the formation of inversions adjacent to the break sites. It is postulated that the disappearance of chromatid breaks with time results from the completion of such rearrangements, rather than from the rejoining of DSB. Elevated frequencies of chromatid breaks occur in irradiated cells with defects in both nonhomologous end-joining (NHEJ) and homologous recombination (HR) pathways, however there is little evidence of a correlation between reduced DSB rejoining and disappearance of chromatid breaks. Moreover, at least one treatment which abrogates the disappearance of chromatid breaks with time leaves DSB rejoining unaffected. The I-SceI DSB system holds considerable promise for the elucidation of these mechanisms, although the break frequency is relatively low in the cell lines so far derived. Techniques to study and improve such systems are under way in different cell lines. Clearly, much remains to be done to clarify the mechanisms involved in chromatid breakage, but the experimental models are becoming available with which we can begin to answer some of the key questions. Copyright 2003 S. Karger AG, Basel</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/1060089','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/1060089"><span>Induction by alkylating agents of sister chromatid exchanges and chromatid breaks in Fanconi's anemia.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Latt, S A; Stetten, G; Juergens, L A; Buchanan, G R; Gerald, P S</p>
<p>1975-10-01</p>
<p>Sister chromatid exchanges, which may reflect chromosome repair in response to certain types of DNA damage, provide a means of investigating the increased chromosome fragility characteristic of Fanconi's anemia. By a recently developed technique using 33258 Hoechst and 5-bromodeoxyuridine, it was observed that the baseline frequency of sister chromatid exchanges in phytohemagglutinin-stimulated lymphocytes from four males with Fanconi's anemia differed little from that of normal lymphocytes. However, addition of the bifunctional alkylating agent mitomycin C (0.01 or 0.03 mug/ml) to the Fanconi's anemia cells during culture induces less than half of the increase in exchanges found in identically treated normal lymphocytes. This reduced increment in exchanges in accompanied by a partial suppression of mitosis and a marked increase in chromatid breaks and rearrangements. Many of these events occur at sites of incomplete chromatid interchange. The increase in sister chromatid exchanges induced in Fanconi's anemia lymphocytes by the monofunctional alkylating agent ethylmethane sulfonate (0.25 mg/ml) was slightly less than that in normal cells. Lymphocytes from two sets of parents of the patients with Fanconi's anemia exhibited a normal response to alkylating agents, while dermal fibroblasts from two different patients with Fanconi's anemia reacted to mitomycin C with an increase in chromatid breaks, but a nearly normal increment of sister chromatid exchanges. The results suggest that chromosomal breaks and rearrangements in Fanconi's anemia lymphocytes may result from a defect in a form of repair of DNA damage.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://eric.ed.gov/?q=recombination&pg=4&id=EJ384605','ERIC'); return false;" href="https://eric.ed.gov/?q=recombination&pg=4&id=EJ384605"><span>How-to-Do-It: Demonstrating Sister Chromatid Exchanges.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p>
<p>Dye, Frank J.</p>
<p>1988-01-01</p>
<p>Outlines procedures for demonstrating and preparing a permanent slide of sister chromatid exchanges and recombination events between the two chromatids of a single chromosome. Provides the name of an additional resource for making preparations of exchanges. (RT)</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=20040088536&hterms=incubation&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D60%26Ntt%3Dincubation','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=20040088536&hterms=incubation&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D60%26Ntt%3Dincubation"><span>Kinetics of chromatid break repair in G2-human fibroblasts exposed to low- and high-LET radiations</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p>
<p>Kawata, T.; Durante, M.; George, K.; Furusawa, Y.; Gotoh, E.; Takai, N.; Wu, H.; Cucinotta, F. A.</p>
<p>2001-01-01</p>
<p>The purpose of this study is to determine the kinetics of chromatid break rejoining following exposure to radiations of different quality. Exponentially growing human fibroblast cells AG1522 were irradiated with gamma-rays, energetic carbon (290 MeV/u), silicon (490 MeV/u) and iron (200 MeV/u, 600 MeV/u). Chromosomes were prematurely condensed using calyculin A. Prematurely condensed chromosomes were collected after several post-irradiation incubation times, ranging from 5 to 600 minutes, and the number of chromatid breaks and exchanges in G2 cells were scored. The relative biological effectiveness (RBE) for initial chromatid breaks per unit dose showed LET dependency having a peak at 55 keV/micrometers silicon (2.4) or 80 keV/micrometers carbon particles (2.4) and then decreased with increasing LET. The kinetics of chromatid break rejoining following low- or high-LET irradiation consisted of two exponential components. Chromatid breaks decreased rapidly after exposure, and then continued to decrease at a slower rate. The rejoining kinetics was similar for exposure to each type of radiation, although the rate of unrejoined breaks was higher for high-LET radiation. Chromatid exchanges were also formed quickly.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11444040','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11444040"><span>Splitting the chromosome: cutting the ties that bind sister chromatids.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Nasmyth, K; Peters, J M; Uhlmann, F</p>
<p>2001-01-01</p>
<p>In eukaryotic cells, replicated DNA molecules remain physically connected from their synthesis in S phase until they are separated during anaphase. This phenomenon, called sister chromatid cohesion, is essential for the temporal separation of DNA replication and mitosis and for the equal separation of the duplicated genome. Recent work has identified a number of chromosomal proteins required for cohesion. In this review we discuss how these proteins may connect sister chromatids and how they are removed from chromosomes to allow sister chromatid separation at the onset of anaphase.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23970416','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23970416"><span>DNA asymmetry in stem cells - immortal or mortal?</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Yadlapalli, Swathi; Yamashita, Yukiko M</p>
<p>2013-09-15</p>
<p>The immortal strand hypothesis proposes that stem cells retain a template copy of genomic DNA (i.e. an 'immortal strand') to avoid replication-induced mutations. An alternative hypothesis suggests that certain cells segregate sister chromatids non-randomly to transmit distinct epigenetic information. However, this area of research has been highly controversial, with conflicting data even from the same cell types. Moreover, historically, the same term of 'non-random sister chromatid segregation' or 'biased sister chromatid segregation' has been used to indicate distinct biological processes, generating a confusion in the biological significance and potential mechanism of each phenomenon. Here, we discuss the models of non-random sister chromatid segregation, and we explore the strengths and limitations of the various techniques and experimental model systems used to study this question. We also describe our recent study on Drosophila male germline stem cells, where sister chromatids of X and Y chromosomes are segregated non-randomly during cell division. We aim to integrate the existing evidence to speculate on the underlying mechanisms and biological relevance of this long-standing observation on non-random sister chromatid segregation.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3772383','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3772383"><span>DNA asymmetry in stem cells – immortal or mortal?</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Yadlapalli, Swathi; Yamashita, Yukiko M.</p>
<p>2013-01-01</p>
<p>Summary The immortal strand hypothesis proposes that stem cells retain a template copy of genomic DNA (i.e. an ‘immortal strand’) to avoid replication-induced mutations. An alternative hypothesis suggests that certain cells segregate sister chromatids non-randomly to transmit distinct epigenetic information. However, this area of research has been highly controversial, with conflicting data even from the same cell types. Moreover, historically, the same term of ‘non-random sister chromatid segregation’ or ‘biased sister chromatid segregation’ has been used to indicate distinct biological processes, generating a confusion in the biological significance and potential mechanism of each phenomenon. Here, we discuss the models of non-random sister chromatid segregation, and we explore the strengths and limitations of the various techniques and experimental model systems used to study this question. We also describe our recent study on Drosophila male germline stem cells, where sister chromatids of X and Y chromosomes are segregated non-randomly during cell division. We aim to integrate the existing evidence to speculate on the underlying mechanisms and biological relevance of this long-standing observation on non-random sister chromatid segregation. PMID:23970416</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=317234','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=317234"><span>Faithful anaphase is ensured by Mis4, a sister chromatid cohesion molecule required in S phase and not destroyed in G1 phase</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Furuya, Kanji; Takahashi, Kohta; Yanagida, Mitsuhiro</p>
<p>1998-01-01</p>
<p>The loss of sister chromatid cohesion triggers anaphase spindle movement. The budding yeast Mcd1/Scc1 protein, called cohesin, is required for associating chromatids, and proteins homologous to it exist in a variety of eukaryotes. Mcd1/Scc1 is removed from chromosomes in anaphase and degrades in G1. We show that the fission yeast protein, Mis4, which is required for equal sister chromatid separation in anaphase is a different chromatid cohesion molecule that behaves independent of cohesin and is conserved from yeast to human. Its inactivation in G1 results in cell lethality in S phase and subsequent premature sister chromatid separation. Inactivation in G2 leads to cell death in subsequent metaphase–anaphase progression but missegregation occurs only in the next round of mitosis. Mis4 is not essential for condensation, nor does it degrade in G1. Rather, it associates with chromosomes in a punctate fashion throughout the cell cycle. mis4 mutants are hypersensitive to hydroxyurea (HU) and UV irradiation but retain the ability to restrain cell cycle progression when damaged or sustaining a block to replication. The mis4 mutation results in synthetic lethality with a DNA ligase mutant. Mis4 may form a stable link between chromatids in S phase that is split rather than removed in anaphase. PMID:9808627</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11862455','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11862455"><span>Colchicine promotes a change in chromosome structure without loss of sister chromatid cohesion in prometaphase I-arrested bivalents.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Rodríguez, E M; Parra, M T; Rufas, J S; Suja, J A</p>
<p>2001-12-01</p>
<p>In somatic cells colchicine promotes the arrest of cell division at prometaphase, and chromosomes show a sequential loss of sister chromatid arm and centromere cohesion. In this study we used colchicine to analyse possible changes in chromosome structure and sister chromatid cohesion in prometaphase I-arrested bivalents of the katydid Pycnogaster cucullata. After silver staining we observed that in colchicine-arrested prometaphase I bivalents, and in contrast to what was found in control bivalents, sister kinetochores appeared individualised and sister chromatid axes were completely separated all along their length. However, this change in chromosome structure occurred without loss of sister chromatid arm cohesion. We also employed the MPM-2 monoclonal antibody against mitotic phosphoproteins on control and colchicine-treated spermatocytes. In control metaphase I bivalents this antibody labelled the tightly associated sister kinetochores and the interchromatid domain. By contrast, in colchicine-treated prometaphase I bivalents individualised sister kinetochores appeared labelled, but the interchromatid domain did not show labelling. These results support the notion that MPM-2 phosphoproteins, probably DNA topoisomerase IIalpha, located in the interchromatid domain act as "chromosomal staples" associating sister chromatid axes in metaphase I bivalents. The disappearance of these chromosomal staples would induce a change in chromosome structure, as reflected by the separation of sister kinetochores and sister axes, but without a concomitant loss of sister chromatid cohesion.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4214429','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4214429"><span>Alternative meiotic chromatid segregation in the holocentric plant Luzula elegans</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Heckmann, Stefan; Jankowska, Maja; Schubert, Veit; Kumke, Katrin; Ma, Wei; Houben, Andreas</p>
<p>2014-01-01</p>
<p>Holocentric chromosomes occur in a number of independent eukaryotic lineages. They form holokinetic kinetochores along the entire poleward chromatid surfaces, and owing to this alternative chromosome structure, species with holocentric chromosomes cannot use the two-step loss of cohesion during meiosis typical for monocentric chromosomes. Here we show that the plant Luzula elegans maintains a holocentric chromosome architecture and behaviour throughout meiosis, and in contrast to monopolar sister centromere orientation, the unfused holokinetic sister centromeres behave as two distinct functional units during meiosis I, resulting in sister chromatid separation. Homologous non-sister chromatids remain terminally linked after metaphase I, by satellite DNA-enriched chromatin threads, until metaphase II. They then separate at anaphase II. Thus, an inverted sequence of meiotic sister chromatid segregation occurs. This alternative meiotic process is most likely one possible adaptation to handle a holocentric chromosome architecture and behaviour during meiosis. PMID:25296379</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25961503','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25961503"><span>Condensin confers the longitudinal rigidity of chromosomes.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Houlard, Martin; Godwin, Jonathan; Metson, Jean; Lee, Jibak; Hirano, Tatsuya; Nasmyth, Kim</p>
<p>2015-06-01</p>
<p>In addition to inter-chromatid cohesion, mitotic and meiotic chromatids must have three physical properties: compaction into 'threads' roughly co-linear with their DNA sequence, intra-chromatid cohesion determining their rigidity, and a mechanism to promote sister chromatid disentanglement. A fundamental issue in chromosome biology is whether a single molecular process accounts for all three features. There is universal agreement that a pair of Smc-kleisin complexes called condensin I and II facilitate sister chromatid disentanglement, but whether they also confer thread formation or longitudinal rigidity is either controversial or has never been directly addressed respectively. We show here that condensin II (beta-kleisin) has an essential role in all three processes during meiosis I in mouse oocytes and that its function overlaps with that of condensin I (gamma-kleisin), which is otherwise redundant. Pre-assembled meiotic bivalents unravel when condensin is inactivated by TEV cleavage, proving that it actually holds chromatin fibres together.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('http://hdl.handle.net/2060/20170009516','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/20170009516"><span>Kits for Characterization of Chromosomal Inversions Using Probes</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p>
<p>Ray, F. Andrew (Inventor)</p>
<p>2017-01-01</p>
<p>A kit for the characterization of chromosomal inversions using single-stranded probes that are either all identical or all complementary to a single-stranded chromatid is described. Reporter species are attached to oligonucleotide strands designed such that they may hybridize to portions of only one of a pair of single-stranded sister chromatids which may be prepared by the CO-FISH procedure. If an inversion has occurred, these marker probes will be detected on the second sister chromatid at the same location as the inversion on the first chromatid. The kit includes non-repetitive probes that are either all identical or all complementary to at least a portion of a target DNA sequence of only one DNA strand of only one chromatid and may in some embodiments include reagents suitable for performing CO-FISH and/or reagents for hybridizing the probes to the target DNA sequence.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3469440','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3469440"><span>Meiosis in male Drosophila</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>McKee, Bruce D.; Yan, Rihui; Tsai, Jui-He</p>
<p>2012-01-01</p>
<p>Meiosis entails sorting and separating both homologous and sister chromatids. The mechanisms for connecting sister chromatids and homologs during meiosis are highly conserved and include specialized forms of the cohesin complex and a tightly regulated homolog synapsis/recombination pathway designed to yield regular crossovers between homologous chromatids. Drosophila male meiosis is of special interest because it dispenses with large segments of the standard meiotic script, particularly recombination, synapsis and the associated structures. Instead, Drosophila relies on a unique protein complex composed of at least two novel proteins, SNM and MNM, to provide stable connections between homologs during meiosis I. Sister chromatid cohesion in Drosophila is mediated by cohesins, ring-shaped complexes that entrap sister chromatids. However, unlike other eukaryotes Drosophila does not rely on the highly conserved Rec8 cohesin in meiosis, but instead utilizes two novel cohesion proteins, ORD and SOLO, which interact with the SMC1/3 cohesin components in providing meiotic cohesion. PMID:23087836</p>
</li>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('http://hdl.handle.net/2060/20150014994','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/20150014994"><span>Characterization of Chromosomal Inversions Using Anti-Parallel Probes</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p>
<p>Ray, F. Andrew (Inventor)</p>
<p>2015-01-01</p>
<p>A method for the characterization of chromosomal inversions using anti-parallel probes is described. Reporter species are attached to oligonucleotide strands designed such that they may hybridize to portions of only one of a pair of single-stranded sister chromatids which may be prepared by the CO-FISH procedure. If an inversion has occurred, these marker probes will be detected on the second sister chromatid at the same location as the inversion on the first chromatid. Further, one or more reporter species are replaced with anti-parallel probes that hybridize at known locations along the second sister chromatid such that the position and size of the inversion may be identified/estimated.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/12020436','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/12020436"><span>Induction and disappearance of G2 chromatid breaks in lymphocytes after low doses of low-LET gamma-rays and high-LET fast neutrons.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Vral, A; Thierens, H; Baeyens, A; De Ridder, L</p>
<p>2002-04-01</p>
<p>To determine by means of the G2 assay the number of chromatid breaks induced by low-LET gamma-rays and high-LET neutrons, and to compare the kinetics of chromatid break rejoining for radiations of different quality. The G2 assay was performed on blood samples of four healthy donors who were irradiated with low-LET gamma-rays and high-LET neutrons. In a first set of experiments a dose-response curve for the formation of chromatid breaks was carried out for gamma-rays and neutrons with doses ranging between 0.1 and 0.5 Gy. In a second set of experiments, the kinetics of chromatid break formation and disappearance were investigated after a dose of 0.5 Gy using post-irradiation times ranging between 0.5 and 3.5 h. For the highest dose of 0.5 Gy, the number of isochromatid breaks was also scored. No significant differences in the number of chromatid breaks were observed between low-LET gamma-rays and high-LET neutrons for the four donors at any of the doses given. The dose-response curves for the formation of chromatid breaks are linear for both radiation qualities and RBEs = 1 were obtained. Scoring of isochromatid breaks at the highest dose of 0.5 Gy revealed that high-LET neutrons were, however, more effective at inducing isochromatid breaks (RBE = 6.2). The rejoining experiments further showed that the kinetics of disappearance of chromatid breaks following irradiation with low-LET gamma-rays or high-LET neutrons were not significantly different. Half-times of 0.92 h for gamma-rays and 0.84 h for neutrons were obtained. Applying the G2 assay, the results demonstrate that at low doses of irradiation, the induction as well as the disappearance of chromatid breaks is independent of the LET of the radiation qualities used (0.24 keV x microm(-1) 60Co gamma-rays and 20 keV x microm(-1) fast neutrons). As these radiation qualities produce the same initial number of double-strand breaks, the results support the signal model that proposes that chromatid breaks are the result of an exchange process which is triggered by a single double-strand break.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/8632802','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/8632802"><span>Cut2 proteolysis required for sister-chromatid seperation in fission yeast.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Funabiki, H; Yamano, H; Kumada, K; Nagao, K; Hunt, T; Yanagida, M</p>
<p>1996-05-30</p>
<p>Although mitotic cyclins are well-known substrates for ubiquitin-mediated proteolysis at the metaphase-anaphase transition, their degradation is not essential for separation of sister chromatids; several lines of evidence suggest that proteolysis of other protein(s) is required, however. Here we report the anaphase-specific proteolysis of the Schizosaccharomyces pombe Cut2 protein, which is essential for sister-chromatid separation. Cut2 is located in the nucleus, where it is concentrated along the short metaphase spindle. The rapid degradation of Cut2 at anaphase requires its amino-terminal region and the activity of Cut9 (ref. 14), a component of the 20S cyclosome/anaphase-promoting complex (APC), which is necessary for cyclin destruction. Expression of non-degradable Cut2 blocks sister-chromatid separation but not cell-cycle progression. This defect can be overcome by grafting the N terminus of cyclin B onto the truncated Cut2, demonstrating that the regulated proteolysis of Cut2 is essential for sister-chromatid separation.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=20060003825&hterms=ito&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D40%26Ntt%3Dito','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=20060003825&hterms=ito&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D40%26Ntt%3Dito"><span>G2 Chromatid Damage and Repair Kinetics in Normal Human Fibroblast Cells Exposed to Low-or High-LET Radiation</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p>
<p>Kawata, T.; Ito, H.; Uno, T.; Saito, M.; Yamamoto, S.; Furusawa, Y.; Durante, M.; George, K.; Wu, H.; Cucinotta, F. A.</p>
<p>2004-01-01</p>
<p>Radiation-induced chromosome damage can be measured in interphase using the Premature Chromosome Condensation (PCC) technique. With the introduction of a new PCC technique using the potent phosphatase inhibitor calyculin-A, chromosomes can be condensed within five minutes, and it is now possible to examine the early damage induced by radiation. Using this method, it has been shown that high-LET radiation induces a higher frequency of chromatid breaks and a much higher frequency of isochromatid breaks than low-LET radiation. The kinetics of chromatid break rejoining consists of two exponential components representing a rapid and a slow time constant, which appears to be similar for low- and high- LET radiations. However, after high-LET radiation exposures, the rejoining process for isochromatid breaks influences the repair kinetics of chromatid-type breaks, and this plays an important role in the assessment of chromatid break rejoining in the G2 phase of the cell cycle.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19066927','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19066927"><span>Influence of the bystander phenomenon on the chromosome aberration pattern in human lymphocytes induced by in vitro alpha-particle exposure.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Schmid, Ernst; Roos, H</p>
<p>2009-04-01</p>
<p>A recent publication on both chromosome-type and chromatid-type aberrations in lymphocytes of patients during treatment with radium-224 for ankylosing spondilitis has revived the question of whether the chromatid-type aberrations may be the consequence of factors released by irradiated cells. Therefore, the aim of the present study was to investigate the influence of such a bystander phenomenon on the chromosome aberration pattern of lymphocytes. Monolayers of human lymphocytes were irradiated with 1 Gy of alpha-particles from an americium-241 source in the absence or presence of whole blood, autologous plasma or culture medium. In the presence of any liquid covering the monolayer during irradiation, the chromatid-type aberrations were, contrary to expectation, elevated. Whereas the intercellular distribution of dicentrics was significantly overdispersed, the chromatid-type aberrations showed a regular dispersion. It can be concluded that the enhanced frequency of chromatid aberrations is the result of a damage signal or a bystander phenomenon released by irradiated cells.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2969851','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2969851"><span>BubR1- and Polo-Coated DNA Tethers Facilitate Poleward Segregation of Acentric Chromatids</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Royou, Anne; Gagou, Mary E.; Karess, Roger; Sullivan, William</p>
<p>2010-01-01</p>
<p>Summary The mechanisms that safeguard cells against chromosomal instability (CIN) are of great interest, as CIN contributes to tumorigenesis. To gain insight into these mechanisms, we studied the behavior of cells entering mitosis with damaged chromosomes. We used the endonuclease I-CreI to generate acentric chromosomes in Drosophila larvae. While I-CreI expression produces acentric chromosomes in the majority of neuronal stem cells, remarkably, it has no effect on adult survival. Our live studies reveal that acentric chromatids segregate efficiently to opposite poles. The acentric chromatid poleward movement is mediated through DNA tethers decorated with BubR1, Polo, INCENP, and Aurora-B. Reduced BubR1 or Polo function results in abnormal segregation of acentric chromatids, a decrease in acentric chromosome tethering, and a great reduction in adult survival. We propose that BubR1 and Polo facilitate the accurate segregation of acentric chromatids by maintaining the integrity of the tethers that connect acentric chromosomes to their centric partners. PMID:20141837</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=20040141465&hterms=incubation&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D70%26Ntt%3Dincubation','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=20040141465&hterms=incubation&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D70%26Ntt%3Dincubation"><span>High-LET radiation-induced aberrations in prematurely condensed G2 chromosomes of human fibroblasts</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p>
<p>Kawata, T.; Gotoh, E.; Durante, M.; Wu, H.; George, K.; Furusawa, Y.; Cucinotta, F. A.; Dicello, J. F. (Principal Investigator)</p>
<p>2000-01-01</p>
<p>PURPOSE: To determine the number of initial chromatid breaks induced by low- or high-LET irradiations, and to compare the kinetics of chromatid break rejoining for radiations of different quality. MATERIAL AND METHODS: Exponentially growing human fibroblast cells AG1522 were irradiated with gamma-rays, energetic carbon (290MeV/u), silicon (490MeV/u) and iron (200 and 600 MeV/u). Chromosomes were prematurely condensed using calyculin A. Chromatid breaks and exchanges in G2 cells were scored. PCC were collected after several post-irradiation incubation times, ranging from 5 to 600 min. RESULTS: The kinetics of chromatid break rejoining following low- or high-LET irradiation consisted of two exponential components representing a rapid and a slow time constant. Chromatid breaks decreased rapidly during the first 10min after exposure, then continued to decrease at a slower rate. The rejoining kinetics were similar for exposure to each type of radiation. Chromatid exchanges were also formed quickly. Compared to low-LET radiation, isochromatid breaks were produced more frequently and the proportion of unrejoined breaks was higher for high-LET radiation. CONCLUSIONS: Compared with gamma-rays, isochromatid breaks were observed more frequently in high-LET irradiated samples, suggesting that an increase in isochromatid breaks is a signature of high-LET radiation exposure.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2776007','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2776007"><span>Effect of borax on immune cell proliferation and sister chromatid exchange in human chromosomes</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Pongsavee, Malinee</p>
<p>2009-01-01</p>
<p>Background Borax is used as a food additive. It becomes toxic when accumulated in the body. It causes vomiting, fatigue and renal failure. Methods The heparinized blood samples from 40 healthy men were studied for the impact of borax toxicity on immune cell proliferation (lymphocyte proliferation) and sister chromatid exchange in human chromosomes. The MTT assay and Sister Chromatid Exchange (SCE) technic were used in this experiment with the borax concentrations of 0.1, 0.15, 0.2, 0.3 and 0.6 mg/ml. Results It showed that the immune cell proliferation (lymphocyte proliferation) was decreased when the concentrations of borax increased. The borax concentration of 0.6 mg/ml had the most effectiveness to the lymphocyte proliferation and had the highest cytotoxicity index (CI). The borax concentrations of 0.15, 0.2, 0.3 and 0.6 mg/ml significantly induced sister chromatid exchange in human chromosomes (P < 0.05). Conclusion Borax had effects on immune cell proliferation (lymphocyte proliferation) and induced sister chromatid exchange in human chromosomes. Toxicity of borax may lead to cellular toxicity and genetic defect in human. PMID:19878537</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28781233','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28781233"><span>Phospho-H1 Decorates the Inter-chromatid Axis and Is Evicted along with Shugoshin by SET during Mitosis.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Krishnan, Swathi; Smits, Arne H; Vermeulen, Michiel; Reinberg, Danny</p>
<p>2017-08-17</p>
<p>Precise control of sister chromatid separation during mitosis is pivotal to maintaining genomic integrity. Yet, the regulatory mechanisms involved are not well understood. Remarkably, we discovered that linker histone H1 phosphorylated at S/T18 decorated the inter-chromatid axial DNA on mitotic chromosomes. Sister chromatid resolution during mitosis required the eviction of such H1S/T18ph by the chaperone SET, with this process being independent of and most likely downstream of arm-cohesin dissociation. SET also directed the disassembly of Shugoshins in a polo-like kinase 1-augmented manner, aiding centromere resolution. SET ablation compromised mitotic fidelity as evidenced by unresolved sister chromatids with marked accumulation of H1S/T18ph and centromeric Shugoshin. Thus, chaperone-assisted eviction of linker histones and Shugoshins is a fundamental step in mammalian mitotic progression. Our findings also elucidate the functional implications of the decades-old observation of mitotic linker histone phosphorylation, serving as a paradigm to explore the role of linker histones in bio-signaling processes. Copyright © 2017 Elsevier Inc. All rights reserved.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=20040112536&hterms=Furusawa&qs=N%3D0%26Ntk%3DAuthor-Name%26Ntx%3Dmode%2Bmatchall%26Ntt%3DFurusawa%252C%2BM','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=20040112536&hterms=Furusawa&qs=N%3D0%26Ntk%3DAuthor-Name%26Ntx%3Dmode%2Bmatchall%26Ntt%3DFurusawa%252C%2BM"><span>Dose--response of initial G2-chromatid breaks induced in normal human fibroblasts by heavy ions</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p>
<p>Kawata, T.; Durante, M.; Furusawa, Y.; George, K.; Takai, N.; Wu, H.; Cucinotta, F. A.; Dicello, J. F. (Principal Investigator)</p>
<p>2001-01-01</p>
<p>PURPOSE: To investigate initial chromatid breaks in prematurely condensed G2 chromosomes following exposure to heavy ions of different LET. MATERIAL AND METHODS: Exponentially growing human fibroblast cells AG1522 were irradiated with gamma-rays, energetic carbon (13 keV/ microm, 80 keV/microm), silicon (55 keV/microm) and iron (140 keV/microm, 185keV/microm, 440keV/microm) ions. Chromosomes were prematurely condensed using calyculin-A. Initial chromatid-type and isochromatid breaks in G2 cells were scored. RESULTS: The dose response curves for total chromatid breaks were linear regardless of radiation type. The relative biological effectiveness (RBE) showed a LET-dependent increase, peaking around 2.7 at 55-80keV/microm and decreasing at higher LET. The dose response curves for isochromatid-type breaks were linear for high-LET radiations, but linear-quadratic for gamma-rays and 13 keV/microm carbon ions. The RBE for the induction of isochromatid breaks obtained from linear components increased rapidly between 13keV/microm (about 7) and 80keV/microm carbon (about 71), and decreased gradually until 440 keV/microm iron ions (about 66). CONCLUSIONS: High-LET radiations are more effective at inducing isochromatid breaks, while low-LET radiations are more effective at inducing chromatid-type breaks. The densely ionizing track structures of heavy ions and the proximity of sister chromatids in G2 cells result in an increase in isochromatid breaks.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27527863','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27527863"><span>Radiation induces premature chromatid separation via the miR-142-3p/Bod1 pathway in carcinoma cells.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Pan, Dong; Du, Yarong; Ren, Zhenxin; Chen, Yaxiong; Li, Xiaoman; Wang, Jufang; Hu, Burong</p>
<p>2016-09-13</p>
<p>Radiation-induced genomic instability plays a vital role in carcinogenesis. Bod1 is required for proper chromosome biorientation, and Bod1 depletion increases premature chromatid separation. MiR-142-3p influences cell cycle progression and inhibits proliferation and invasion in cervical carcinoma cells. We found that radiation induced premature chromatid separation and altered miR-142-3p and Bod1 expression in 786-O and A549 cells. Overexpression of miR-142-3p increased premature chromatid separation and G2/M cell cycle arrest in 786-O cells by suppressing Bod1 expression. We also found that either overexpression of miR-142-3p or knockdown of Bod1 sensitized 786-O and A549 cells to X-ray radiation. Overexpression of Bod1 inhibited radiation- and miR-142-3p-induced premature chromatid separation and increased resistance to radiation in 786-O and A549 cells. Taken together, these results suggest that radiation alters miR-142-3p and Bod1 expression in carcinoma cells, and thus contributes to early stages of radiation-induced genomic instability. Combining ionizing radiation with epigenetic regulation may help improve cancer therapies.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/1585081','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/1585081"><span>Effect of chloramphenicol on sister chromatid exchange in bovine fibroblasts.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Arruga, M V; Catalan, J; Moreno, C</p>
<p>1992-03-01</p>
<p>The genotoxic potential of different chloramphenicol concentrations (5, 20, 40 and 60 micrograms ml-1) was investigated in bovine fibroblast primary lines by sister chromatid exchange assay. Chloramphenicol acted for long enough to ensure similar effects to persistent storage in the kidney. In this experiment 10 micrograms ml-1 of 5-bromodeoxyuridine was added for 60 hours for all doses of chloramphenicol and to the control. When the tissue culture cells were exposed to increasing doses, increased numbers of sister chromatid exchanges developed. Differences were significantly different to the control.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3674063','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3674063"><span>Sister chromatid segregation in meiosis II</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Wassmann, Katja</p>
<p>2013-01-01</p>
<p>Meiotic divisions (meiosis I and II) are specialized cell divisions to generate haploid gametes. The first meiotic division with the separation of chromosomes is named reductional division. The second division, which takes place immediately after meiosis I without intervening S-phase, is equational, with the separation of sister chromatids, similar to mitosis. This meiotic segregation pattern requires the two-step removal of the cohesin complex holding sister chromatids together: cohesin is removed from chromosome arms that have been subjected to homologous recombination in meiosis I and from the centromere region in meiosis II. Cohesin in the centromere region is protected from removal in meiosis I, but this protection has to be removed—deprotected”—for sister chromatid segregation in meiosis II. Whereas the mechanisms of cohesin protection are quite well understood, the mechanisms of deprotection have been largely unknown until recently. In this review I summarize our current knowledge on cohesin deprotection. PMID:23574717</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4190664','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4190664"><span>Chiasmatic and achiasmatic inverted meiosis of plants with holocentric chromosomes</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Cabral, Gabriela; Marques, André; Schubert, Veit; Pedrosa-Harand, Andrea; Schlögelhofer, Peter</p>
<p>2014-01-01</p>
<p>Meiosis is a specialized cell division in sexually reproducing organisms before gamete formation. Following DNA replication, the canonical sequence in species with monocentric chromosomes is characterized by reductional segregation of homologous chromosomes during the first and equational segregation of sister chromatids during the second meiotic division. Species with holocentric chromosomes employ specific adaptations to ensure regular disjunction during meiosis. Here we present the analysis of two closely related plant species with holocentric chromosomes that display an inversion of the canonical meiotic sequence, with the equational division preceding the reductional. In-depth analysis of the meiotic divisions of Rhynchospora pubera and R. tenuis reveals that during meiosis I sister chromatids are bi-oriented, display amphitelic attachment to the spindle and are subsequently separated. During prophase II, chromatids are connected by thin chromatin threads that appear instrumental for the regular disjunction of homologous non-sister chromatids in meiosis II. PMID:25295686</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26122845','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26122845"><span>Defects in the Fanconi Anemia Pathway and Chromatid Cohesion in Head and Neck Cancer.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Stoepker, Chantal; Ameziane, Najim; van der Lelij, Petra; Kooi, Irsan E; Oostra, Anneke B; Rooimans, Martin A; van Mil, Saskia E; Brink, Arjen; Dietrich, Ralf; Balk, Jesper A; Ylstra, Bauke; Joenje, Hans; Feller, Stephan M; Brakenhoff, Ruud H</p>
<p>2015-09-01</p>
<p>Failure to repair DNA damage or defective sister chromatid cohesion, a process essential for correct chromosome segregation, can be causative of chromosomal instability (CIN), which is a hallmark of many types of cancers. We investigated how frequent this occurs in head and neck squamous cell carcinoma (HNSCC) and whether specific mechanisms or genes could be linked to these phenotypes. The genomic instability syndrome Fanconi anemia is caused by mutations in any of at least 16 genes regulating DNA interstrand crosslink (ICL) repair. Since patients with Fanconi anemia have a high risk to develop HNSCC, we investigated whether and to which extent Fanconi anemia pathway inactivation underlies CIN in HNSCC of non-Fanconi anemia individuals. We observed ICL-induced chromosomal breakage in 9 of 17 (53%) HNSCC cell lines derived from patients without Fanconi anemia. In addition, defective sister chromatid cohesion was observed in five HNSCC cell lines. Inactivation of FANCM was responsible for chromosomal breakage in one cell line, whereas in two other cell lines, somatic mutations in PDS5A or STAG2 resulted in inadequate sister chromatid cohesion. In addition, FANCF methylation was found in one cell line by screening an additional panel of 39 HNSCC cell lines. Our data demonstrate that CIN in terms of ICL-induced chromosomal breakage and defective chromatid cohesion is frequently observed in HNSCC. Inactivation of known Fanconi anemia and chromatid cohesion genes does explain CIN in the minority of cases. These findings point to phenotypes that may be highly relevant in treatment response of HNSCC. ©2015 American Association for Cancer Research.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3899872','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3899872"><span>The energy components of stacked chromatin layers explain the morphology, dimensions and mechanical properties of metaphase chromosomes</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Daban, Joan-Ramon</p>
<p>2014-01-01</p>
<p>The measurement of the dimensions of metaphase chromosomes in different animal and plant karyotypes prepared in different laboratories indicates that chromatids have a great variety of sizes which are dependent on the amount of DNA that they contain. However, all chromatids are elongated cylinders that have relatively similar shape proportions (length to diameter ratio approx. 13). To explain this geometry, it is considered that chromosomes are self-organizing structures formed by stacked layers of planar chromatin and that the energy of nucleosome–nucleosome interactions between chromatin layers inside the chromatid is approximately 3.6 × 10−20 J per nucleosome, which is the value reported by other authors for internucleosome interactions in chromatin fibres. Nucleosomes in the periphery of the chromatid are in contact with the medium; they cannot fully interact with bulk chromatin within layers and this generates a surface potential that destabilizes the structure. Chromatids are smooth cylinders because this morphology has a lower surface energy than structures having irregular surfaces. The elongated shape of chromatids can be explained if the destabilizing surface potential is higher in the telomeres (approx. 0.16 mJ m−2) than in the lateral surface (approx. 0.012 mJ m−2). The results obtained by other authors in experimental studies of chromosome mechanics have been used to test the proposed supramolecular structure. It is demonstrated quantitatively that internucleosome interactions between chromatin layers can justify the work required for elastic chromosome stretching (approx. 0.1 pJ for large chromosomes). The high amount of work (up to approx. 10 pJ) required for large chromosome extensions is probably absorbed by chromatin layers through a mechanism involving nucleosome unwrapping. PMID:24402918</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=43487&Lab=ORD&keyword=bone&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50','EPA-EIMS'); return false;" href="https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=43487&Lab=ORD&keyword=bone&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50"><span>EVIDENCE FOR THE CHROMOSOMAL REPLICONS AS UNITS OF SISTER CHROMATID EXCHANGES</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://oaspub.epa.gov/eims/query.page">EPA Science Inventory</a></p>
<p></p>
<p></p>
<p>Current hypotheses of sister chromatid exchange (SCE) formation postulate that sites of SCE induction are associated with active replicons or replicon clusters. We have applied the FCC-SCD technique to in vivo studies of mouse bone marrow cells that have been treated with cycloph...</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=39928&Lab=ORD&keyword=infusion&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50','EPA-EIMS'); return false;" href="https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=39928&Lab=ORD&keyword=infusion&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50"><span>INDUCTION, ACCUMULATION, AND PERSISTENCE OF SISTER CHROMATID EXCHANGES IN WOMEN WITH BREAST CANCER RECEIVING CYCLOPHOSPHAMIDE, ANDRIAMYCIN, AND 5-FLUOROACIL CHEMOTHERAPY</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://oaspub.epa.gov/eims/query.page">EPA Science Inventory</a></p>
<p></p>
<p></p>
<p>The induction, stimulation, and persistence of sister chromatid exchanges (SCE's) and high SCE frequency cells (HFC's) was measured in peripheral lymphocytes of women with breast cancer before chemotherapy and on multiple occasions during and after therapy. Chemotherapy consisted...</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/15162039','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/15162039"><span>Complex chromatid-isochromatid exchanges following irradiation with heavy ions?</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Loucas, B D; Eberle, R L; Durante, M; Cornforth, M N</p>
<p>2004-01-01</p>
<p>We describe a peculiar and relatively rare type of chromosomal rearrangement induced in human peripheral lymphocytes that were ostensibly irradiated in G(0) phase of the cell cycle by accelerated heavy ions, and which, to the best of our knowledge, have not been previously described. The novel rearrangements which were detected using mFISH following exposure to 500 MeV/nucleon and 5 GeV/n 56Fe particles, but were not induced by either 137Cs gamma rays or 238Pu alpha particles, can alternatively be described as either complex chromatid-isochromatid or complex chromatid-chromosome exchanges. Different mechanisms potentially responsible for their formation are discussed. Copyright 2003 S. Karger AG, Basel</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25194916','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25194916"><span>"Breaking up is hard to do": the formation and resolution of sister chromatid intertwines.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Baxter, Jonathan</p>
<p>2015-02-13</p>
<p>The absolute necessity to resolve every intertwine between the two strands of the DNA double helix provides a massive challenge to the cellular processes that duplicate and segregate chromosomes. Although the overwhelming majority of intertwines between the parental DNA strands are resolved during DNA replication, there are numerous chromosomal contexts where some intertwining is maintained into mitosis. These mitotic sister chromatid intertwines (SCIs) can be found as; short regions of unreplicated DNA, fully replicated and intertwined sister chromatids--commonly referred to as DNA catenation--and as sister chromatid linkages generated by homologous recombination-associated processes. Several overlapping mechanisms, including intra-chromosomal compaction, topoisomerase action and Holliday junction resolvases, ensure that all SCIs are removed before they can prevent normal chromosome segregation. Here, I discuss why some DNA intertwines persist into mitosis and review our current knowledge of the SCI resolution mechanisms that are employed in both prokaryotes and eukaryotes, including how deregulating SCI formation during DNA replication or disrupting the resolution processes may contribute to aneuploidy in cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25553380','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25553380"><span>Selective chromatid segregation mechanism for Bruchus wings piebald color.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Klar, Amar J S</p>
<p>2015-01-01</p>
<p>The mechanisms of asymmetric organ development have been under intensive investigation for years, yet the proposed mechanisms remain controversial (1-3). The female Bruchus quadrimaculatus beetle insect develops two black-colored spots bilaterally located on each upper elytra wing by an unknown mechanism. Fifty percent of the P (for piebald, two colors) gene homozygous mutant insects, described in 1925, had a normal left elytrum (with two black spots) and an abnormal right elytrum (with two red spots) and the balance supported the converse lateralized pigment arrangement (4). Rather than supporting the conventional morphogen model for the wings pigmentation development, their biological origin is explained here with the somatic strand-specific epigenetic imprinting and selective sister chromatid segregation (SSIS) mechanism (5). We propose that the P gene product performs the selective sister chromatid segregation function to produce symmetric cell division of a specific cell during embryogenesis to result in the bilateral symmetric development of elytra black color spots and that the altered chromatid segregation pattern of the mutant causes asymmetric cell division to confer the piebald phenotype. </p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20142422','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20142422"><span>SOLO: a meiotic protein required for centromere cohesion, coorientation, and SMC1 localization in Drosophila melanogaster.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Yan, Rihui; Thomas, Sharon E; Tsai, Jui-He; Yamada, Yukihiro; McKee, Bruce D</p>
<p>2010-02-08</p>
<p>Sister chromatid cohesion is essential to maintain stable connections between homologues and sister chromatids during meiosis and to establish correct centromere orientation patterns on the meiosis I and II spindles. However, the meiotic cohesion apparatus in Drosophila melanogaster remains largely uncharacterized. We describe a novel protein, sisters on the loose (SOLO), which is essential for meiotic cohesion in Drosophila. In solo mutants, sister centromeres separate before prometaphase I, disrupting meiosis I centromere orientation and causing nondisjunction of both homologous and sister chromatids. Centromeric foci of the cohesin protein SMC1 are absent in solo mutants at all meiotic stages. SOLO and SMC1 colocalize to meiotic centromeres from early prophase I until anaphase II in wild-type males, but both proteins disappear prematurely at anaphase I in mutants for mei-S332, which encodes the Drosophila homologue of the cohesin protector protein shugoshin. The solo mutant phenotypes and the localization patterns of SOLO and SMC1 indicate that they function together to maintain sister chromatid cohesion in Drosophila meiosis.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=86942','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=86942"><span>Saccharomyces cerevisiae CTF18 and CTF4 Are Required for Sister Chromatid Cohesion</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Hanna, Joseph S.; Kroll, Evgueny S.; Lundblad, Victoria; Spencer, Forrest A.</p>
<p>2001-01-01</p>
<p>CTF4 and CTF18 are required for high-fidelity chromosome segregation. Both exhibit genetic and physical ties to replication fork constituents. We find that absence of either CTF4 or CTF18 causes sister chromatid cohesion failure and leads to a preanaphase accumulation of cells that depends on the spindle assembly checkpoint. The physical and genetic interactions between CTF4, CTF18, and core components of replication fork complexes observed in this study and others suggest that both gene products act in association with the replication fork to facilitate sister chromatid cohesion. We find that Ctf18p, an RFC1-like protein, directly interacts with Rfc2p, Rfc3p, Rfc4p, and Rfc5p. However, Ctf18p is not a component of biochemically purified proliferating cell nuclear antigen loading RF-C, suggesting the presence of a discrete complex containing Ctf18p, Rfc2p, Rfc3p, Rfc4p, and Rfc5p. Recent identification and characterization of the budding yeast polymerase κ, encoded by TRF4, strongly supports a hypothesis that the DNA replication machinery is required for proper sister chromatid cohesion. Analogous to the polymerase switching role of the bacterial and human RF-C complexes, we propose that budding yeast RF-CCTF18 may be involved in a polymerase switch event that facilities sister chromatid cohesion. The requirement for CTF4 and CTF18 in robust cohesion identifies novel roles for replication accessory proteins in this process. PMID:11287619</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1469616','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1469616"><span>Cytogenetic Monitoring of Farmers exposed to pesticides in Colombia.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Hoyos, L S; Carvajal, S; Solano, L; Rodriguez, J; Orozco, L; López, Y; Au, W W</p>
<p>1996-01-01</p>
<p>We have monitored 30 pesticide-exposed workers and 30 matched controls for expression of chromosome aberrations (CA) and sister chromatid exchanges (SCE) in their lymphocytes. Peripheral blood cultures were set up within 3 hr after the collection of samples, and four cultures were set up from each donor. For CA analysis, 100 complete metaphase cells from each donor were evaluated. For the SCE assay, 50 complete metaphase cells from each donor were analyzed. The CA and SCE data were analyzed for differences between the two groups using the chi 2 and the Student's t-test, respectively. From the CA analysis it was obvious that the overwhelming majority of aberrations were chromatid breaks and isochromatid breaks; therefore, only these data are presented and used for statistical analysis. Isochromatid breaks were counted as two breaks each and chromatid breaks as one in calculating the total chromatid break frequencies. Statistical evaluation of the data indicates that there is no significant difference (p > 0.05; chi 2 test) between the exposed and the nonexposed groups based on chromatid breaks per 100 cells (1.2 +/- 0.3 and 1.5 +/- 0.2, respectively) and total chromatid breaks per 100 cells (1.7 +/- 0.3 and 2.1 +/- 0.2, respectively). No significantly difference between the two groups (p > 0.05, Student's t-test) was observed with SCE frequencies (5.0 +/- 1.1 and 4.8 +/- 0.9, respectively). Linear regression analysis indicates that the data were not influenced by age, cigarette smoking, or alcohol consumption. It is assuring that the exposure conditions among these Indian farmers have not caused detectable increases of chromosome damage using standard assays; this suggests the lack of serious long-term health problems. However, periodic monitoring of such exposed populations should be conducted using the same or other more sensitive assays. In addition, other populations with exposure to different types of pesticides in Colombia should also be investigated. PMID:8781378</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/133441-pre-implantation-diagnosis-aneuploidy-polar-body-blastomere-fish-analysis','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/133441-pre-implantation-diagnosis-aneuploidy-polar-body-blastomere-fish-analysis"><span>Pre-implantation diagnosis of aneuploidy by polar body and blastomere FISH analysis</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Munne, S.; Cohen, J.; Grifo, J.</p>
<p>1994-09-01</p>
<p>For preimplantation genetic diagnosis (PGD) of aneuploidy in human in-vitro fertilization (IVF), two blastomeres per embryo should be analyzed to minimize errors caused by FISH and mosaicism. But the biopsy of two cells from an 8-cell embryo can be detrimental. This can be substituted by initial FISH analysis of the first polar body (PB) and subsequent single blastomere analysis. Simultaneous FISH analysis of chromosomes X, Y, 18, 13/21 was used for first polar body aneuploidy analysis. Normal divalents appeared as single-dotted signals corresponding to their two chromatids. We found that pre-division of chromatids increased dramatically with time in culture. Allmore » but three pre-division events involved separation of chromatids within the PB or the egg, with a total of two chromatids in each. We concluded that PB aneuploidy analysis is safe when performed within 6 hours after egg retrieval. For our first clinical case we chose a 39 year-old female carrier of an X-linked disease already selected for FISH pre-implantation diagnosis. Eight polar bodies from 12 eggs were analyzed: six showed a normal X181321 complement of divalents; one had an extra chromatid for 13/21 (egg {number_sign}8); and one had a missing chromatid for 13/21 (egg {number_sign}10). After insemination, six fertilized eggs developed into embryos, including egg {number_sign}10 but not egg {number_sign}8. At day 3 of development, a single blastomere per embryo was analyzed by FISH. According to the blastomere analysis, one embryo was haploid, one tetraploid. The two normal female embryos were replaced and pregnancy and CFS results are pending. These results suggest that this technique can be successfully applied for PGD of major aneuploidies in IVF patients over 35. In addition, it indicates that studies on pre-division should be performed on eggs within six hours of retrieval.« less</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5732777','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5732777"><span>PARP inhibition causes premature loss of cohesion in cancer cells</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Kukolj, Eva; Kaufmann, Tanja; Dick, Amalie E.; Zeillinger, Robert; Gerlich, Daniel W.; Slade, Dea</p>
<p>2017-01-01</p>
<p>Poly(ADP-ribose) polymerases (PARPs) regulate various aspects of cellular function including mitotic progression. Although PARP inhibitors have been undergoing various clinical trials and the PARP1/2 inhibitor olaparib was approved as monotherapy for BRCA-mutated ovarian cancer, their mode of action in killing tumour cells is not fully understood. We investigated the effect of PARP inhibition on mitosis in cancerous (cervical, ovary, breast and osteosarcoma) and non-cancerous cells by live-cell imaging. The clinically relevant inhibitor olaparib induced strong perturbations in mitosis, including problems with chromosome alignment at the metaphase plate, anaphase delay, and premature loss of cohesion (cohesion fatigue) after a prolonged metaphase arrest, resulting in sister chromatid scattering. PARP1 and PARP2 depletion suppressed the phenotype while PARP2 overexpression enhanced it, suggesting that olaparib-bound PARP1 and PARP2 rather than the lack of catalytic activity causes this phenotype. Olaparib-induced mitotic chromatid scattering was observed in various cancer cell lines with increased protein levels of PARP1 and PARP2, but not in non-cancer or cancer cell lines that expressed lower levels of PARP1 or PARP2. Interestingly, the sister chromatid scattering phenotype occurred only when olaparib was added during the S-phase preceding mitosis, suggesting that PARP1 and PARP2 entrapment at replication forks impairs sister chromatid cohesion. Clinically relevant DNA-damaging agents that impair replication progression such as topoisomerase inhibitors and cisplatin were also found to induce sister chromatid scattering and metaphase plate alignment problems, suggesting that these mitotic phenotypes are a common outcome of replication perturbation. PMID:29262611</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23700831','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23700831"><span>[Comparative analysis of cytogenetic examination of control groups of subjects carried out in different Russian laboratories].</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Sevan'kaev, A V; Khvostunov, I K; Snigireva, G P; Novitskaia, N N; Antoshchina, M M; Fesenko, E V; Vorobtsova, I E; Neronova, E G; Domracheva, E V; Nugis, V Iu; Govorun, R D; Handogina, E K</p>
<p>2013-01-01</p>
<p>The incidence of unstable chromosome aberrations in peripheral blood lymphocytes from unirradiated control subjects was analyzed using cytogenetic data obtained from 9 cytogenetic laboratories located in Moscow, St.-Petersburg, Obninsk, and Dubna (Russia). The objective of this study was to estimate the level and spectrum of spontaneous chromosome aberrations in human lymphocytes. 1140 blood samples were taken from 1112 subjects (594 men and 546 women) aged 1 to 72. The total metaphase number was 466795. The uniform Giemsa method for peripheral blood lymphocyte cultures was used. After counting 466795 metaphases, 4288 chromosomal aberrations of various types were classified. The most frequent types of aberrations were acentrics and chromatid deletions. They made up 90% of the total number of aberrations. The remaining 10% were exchange aberrations. The number of chromosome exchanges (dicentrics and centric rings) was twice the number of chromatid exchanges. Overall, the portion ofcells with chromosomal or (and) chromatid aberrations was 0.89 +/- 0.01%; the frequency of acentrics was 0.29 +/- 0.01; the frequency of dicentrics was 0.046 +/- 0.003; the frequency of unstable chromosome aberrations was 0.35 +/- 0.01; and the frequency of chromatid aberrations was 0.57 +/- 0.01 per 100 cells.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/1998603','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/1998603"><span>Frequency of sister chromatid exchange and chromosomal aberrations in asbestos cement workers.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Fatma, N; Jain, A K; Rahman, Q</p>
<p>1991-02-01</p>
<p>Exposure to asbestos minerals has been associated with a wide variety of adverse health effects including lung cancer, pleural mesothelioma, and cancer of other organs. It was shown previously that asbestos samples collected from a local asbestos factory enhanced sister chromatid exchanges (SCEs) and chromosomal aberrations in vitro using human lymphocytes. In the present study, 22 workers from the same factory and 12 controls were further investigated. Controls were matched for age, sex, and socioeconomic state. The peripheral blood lymphocytes were cultured and harvested at 48 hours for studies of chromosomal aberrations and at 72 hours for SCE frequency determinations. Asbestos workers had a raised mean SCE rate and increased numbers of chromosomal aberrations compared with a control population. Most of the chromosomal aberrations were chromatid gap and break types.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25213378','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25213378"><span>Sister kinetochores are mechanically fused during meiosis I in yeast.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Sarangapani, Krishna K; Duro, Eris; Deng, Yi; Alves, Flavia de Lima; Ye, Qiaozhen; Opoku, Kwaku N; Ceto, Steven; Rappsilber, Juri; Corbett, Kevin D; Biggins, Sue; Marston, Adèle L; Asbury, Charles L</p>
<p>2014-10-10</p>
<p>Production of healthy gametes requires a reductional meiosis I division in which replicated sister chromatids comigrate, rather than separate as in mitosis or meiosis II. Fusion of sister kinetochores during meiosis I may underlie sister chromatid comigration in diverse organisms, but direct evidence for such fusion has been lacking. We used laser trapping and quantitative fluorescence microscopy to study native kinetochore particles isolated from yeast. Meiosis I kinetochores formed stronger attachments and carried more microtubule-binding elements than kinetochores isolated from cells in mitosis or meiosis II. The meiosis I-specific monopolin complex was both necessary and sufficient to drive these modifications. Thus, kinetochore fusion directs sister chromatid comigration, a conserved feature of meiosis that is fundamental to Mendelian inheritance. Copyright © 2014, American Association for the Advancement of Science.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=61071&keyword=SCG&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50','EPA-EIMS'); return false;" href="https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=61071&keyword=SCG&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50"><span>INVESTIGATION OF DNA REPAIR BY SISTER CHROMATID EXCHANGE (SCE) ANALYSIS AND THE ALKALINE SINGLE CELL GEL ASSAY (SCG) IN MAMMALIAN GO-LYMPHOCYTES AFTER IN VITRO EXPOSURE TO ETHYLENE OXIDE (EO)</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://oaspub.epa.gov/eims/query.page">EPA Science Inventory</a></p>
<p></p>
<p></p>
<p>Investigation ofDNA Repair by Sister Chromatid Exchange (SCE) Analysis and the Alkaline Single Cell Gel Assay (SCG) in Mammalian Go-Lymphocytes after In Vitro Exposure to Ethylene Oxide (EO). <br><br>EO is a large volume chemical used primarily as an intermediate in manufacturing...</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/4069583','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/4069583"><span>Abnormal centromere-chromatid apposition (ACCA) and Peters' anomaly.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Wertelecki, W; Dev, V G; Superneau, D W</p>
<p>1985-08-01</p>
<p>Abnormal centromere-chromatid apposition (ACCA) was noted in a patient with Peters' anomaly. Previous reports of ACCA emphasized its association with tetraphocomelia and other congenital malformations (Roberts, SC Phocomelia, Pseudothalidomide Syndromes). This report expands the array of congenital malformations associated with ACCA and emphasizes the diagnostic importance of ocular defects for the ascertainment of additional cases of ACCA and its possible relationship with abnormal cell division.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=128808','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=128808"><span>Telomere formation on macronuclear chromosomes of Oxytricha trifallax and O. fallax: alternatively processed regions have multiple telomere addition sites</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Williams, Kevin R; Doak, Thomas G; Herrick, Glenn</p>
<p>2002-01-01</p>
<p>Background Ciliates employ massive chromatid breakage and de novo telomere formation during generation of the somatic macronucleus. Positions flanking the 81-MAC locus are reproducibly cut. But those flanking the Common Region are proposed to often escape cutting, generating three nested macronuclear chromosomes, two retaining "arms" still appended to the Common Region. Arm-distal positions must differ (in cis) from the Common Region flanks. Results The Common-Region-flanking positions also differ from the arm-distal positions in that they are "multi-TAS" regions: anchored PCR shows heterogeneous patterns of telomere addition sites, but arm-distal sites do not. The multi-TAS patterns are reproducible, but are sensitive to the sequence of the allele being processed. Thus, random degradation following chromatid cutting does not create this heterogeneity; these telomere addition sites also must be dictated by cis-acting sequences. Conclusions Most ciliates show such micro-heterogeneity in the precise positions of telomere addition sites. Telomerase is believed to be tightly associated with, and act in concert with, the chromatid-cutting nuclease: heterogeneity must be the result of intervening erosion activity. Our "weak-sites" hypothesis explains the correlation between alternative chromatid cutting at the Common Region boundaries and their multi-TAS character: when the chromatid-breakage machine encounters either a weak binding site or a weak cut site at these regions, then telomerase dissociates prematurely, leaving the new end subject to erosion by an exonuclease, which pauses at cis-acting sequences; telomerase eventually heals these resected termini. Finally, we observe TAS positioning influenced by trans-allelic interactions, reminiscent of transvection. PMID:12199911</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22701050','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22701050"><span>The centenary of Janssens's chiasmatype theory.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Koszul, Romain; Meselson, Matthew; Van Doninck, Karine; Vandenhaute, Jean; Zickler, Denise</p>
<p>2012-06-01</p>
<p>The segregation and random assortment of characters observed by Mendel have their basis in the behavior of chromosomes in meiosis. But showing this actually to be the case requires a correct understanding of the meiotic behavior of chromosomes. This was achieved only gradually, over several decades, with much dispute and confusion along the way. One crucial step in the understanding of meiosis was provided in 1909 by Frans Alfons Janssens who published in La Cellule an article entitled "La théorie de la Chiasmatypie. Nouvelle interprétation des cinèses de maturation," which contains the first description of the chiasma structure. He observed that, of the four chromatids present at the connection sites (chiasmata sites) at diplotene or anaphase of the first meiotic division, two crossed each other and two did not. He therefore postulated that the maternal and paternal chromatids that crossed penetrated the other until they broke and rejoined in maternal and paternal segments new ways; the other two chromatids remained free and thus intact. This allowed him also to propose that the chromatids distributed in the four nuclei issued from the second meiotic division had various combinations of maternal and paternal segments of each chromosome. And conversely, permitted the appreciation that the laws of Mendelian segregation required breakage and joining (crossing over) between homologous non-sister chromatids. Although Janssens's article found a broad appreciative audience and had a large influence on the chromosomal theory at that time, his theory was resisted by both geneticists and cytologists for several decades. This Perspectives aims to highlight the novelty of Janssens's chiasmatype theory by examining the historical background and our actual understanding of meiotic recombination.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3374303','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3374303"><span>The Centenary of Janssens’s Chiasmatype Theory</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Koszul, Romain; Meselson, Matthew; Van Doninck, Karine; Vandenhaute, Jean; Zickler, Denise</p>
<p>2012-01-01</p>
<p>The segregation and random assortment of characters observed by Mendel have their basis in the behavior of chromosomes in meiosis. But showing this actually to be the case requires a correct understanding of the meiotic behavior of chromosomes. This was achieved only gradually, over several decades, with much dispute and confusion along the way. One crucial step in the understanding of meiosis was provided in 1909 by Frans Alfons Janssens who published in La Cellule an article entitled “La théorie de la Chiasmatypie. Nouvelle interprétation des cinèses de maturation,” which contains the first description of the chiasma structure. He observed that, of the four chromatids present at the connection sites (chiasmata sites) at diplotene or anaphase of the first meiotic division, two crossed each other and two did not. He therefore postulated that the maternal and paternal chromatids that crossed penetrated the other until they broke and rejoined in maternal and paternal segments new ways; the other two chromatids remained free and thus intact. This allowed him also to propose that the chromatids distributed in the four nuclei issued from the second meiotic division had various combinations of maternal and paternal segments of each chromosome. And conversely, permitted the appreciation that the laws of Mendelian segregation required breakage and joining (crossing over) between homologous non-sister chromatids. Although Janssens’s article found a broad appreciative audience and had a large influence on the chromosomal theory at that time, his theory was resisted by both geneticists and cytologists for several decades. This Perspectives aims to highlight the novelty of Janssens’s chiasmatype theory by examining the historical background and our actual understanding of meiotic recombination. PMID:22701050</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23417411','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23417411"><span>Histone hyperacetylation during meiosis interferes with large-scale chromatin remodeling, axial chromatid condensation and sister chromatid separation in the mammalian oocyte.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Yang, Feikun; Baumann, Claudia; Viveiros, Maria M; De La Fuente, Rabindranath</p>
<p>2012-01-01</p>
<p>Histone acetylation regulates higher-order chromatin structure and function and is critical for the control of gene expression. Histone deacetylase inhibitors (HDACi) are currently under investigation as novel cancer therapeutic drugs. Here, we show that female germ cells are extremely susceptible to chromatin changes induced by HDACi. Our results indicate that exposure to trichostatin A (TSA) at nanomolar levels interferes with major chromatin remodeling events in the mammalian oocyte leading to chromosome instability. High resolution analysis of chromatin structure and live-cell imaging revealed a striking euchromatin decondensation associated with histone H4 hyperacetylation following exposure to 15 nM TSA in >90% of pre-ovulatory oocytes. Dynamic changes in large-scale chromatin structure were detected after 2 h of exposure and result in the formation of misaligned chromosomes in >75% (P<0.05) of in vitro matured oocytes showing chromosome lagging as well as abnormal sister chromatid separation at anaphase I. Abnormal axial chromatid condensation during meiosis results in the formation of elongated chromosomes exhibiting hyperacetylation of histone H4 at lysine 5 and lysine 16 at interstitial chromosome segments, but not pericentric heterochromatin, while highly decondensed bivalents exhibit prominent histone H3 phosphorylation at centromeric domains. Notably, no changes were observed in the chromosomal localization of the condensin protein SMC4. These results indicate that HDAC activity is required for proper chromosome condensation in the mammalian oocyte and that HDACi may induce abnormal chromosome segregation by interfering with both chromosome-microtubule interactions, as well as sister chromatid separation. Thus, HDACi, proposed for cancer therapy, may disrupt the epigenetic status of female germ cells, predisposing oocytes to aneuploidy at previously unrecognized low doses.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1009291','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1009291"><span>Chromosome analysis from peripheral blood lymphocytes of workers after an acute exposure to benzene.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Clare, M G; Yardley-Jones, A; Maclean, A C; Dean, B J</p>
<p>1984-01-01</p>
<p>A spillage of about 1200 gallons of benzene occurred during the loading of a ship, and 10 workers on a single shift were exposed to benzene. Shortly afterwards, an assay of the urine of these individuals showed that substantial amounts of phenol were being excreted. About three months after the incident samples of venous blood were taken from 10 individuals exposed to benzene and 11 men on a comparable shift who acted as controls. The lymphocytes were stimulated to divide in short term cultures. For each subject, 200 cells at metaphase were examined for chromosome damage using 48 h cultures, and sister chromatid exchanges (SCE) were analysed from about 30 cells in their second division, using 72 h cultures. The most frequent types of aberrations in all the individuals were chromatid gaps, with occasional breaks of chromatids and chromosomes. There were few exchanges within or between the arms of chromatids or chromosomes. More cells in the control than in the exposed group showed damage, an effect that was especially noticeable for chromatid gaps. All values, however, were considered to be within a normal range. There were slightly more SCE in some of the exposed individuals than in the controls and there was a trend towards a positive association between the frequency of SCE recorded for each individual and the maximum value for the excretion of phenol in the urine on the day after the incident. There is no evidence to indicate that benzene induced any type of lasting chromosome damage in the lymphocytes of the 10 exposed workers when cells were examined about three months after the incident. PMID:6722051</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=20040112575&hterms=cells+cancer&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D70%26Ntt%3Dcells%2Bcancer','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=20040112575&hterms=cells+cancer&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D70%26Ntt%3Dcells%2Bcancer"><span>Cell killing and chromatid damage in primary human bronchial epithelial cells irradiated with accelerated 56Fe ions</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p>
<p>Suzuki, M.; Piao, C.; Hall, E. J.; Hei, T. K.</p>
<p>2001-01-01</p>
<p>We examined cell killing and chromatid damage in primary human bronchial epithelial cells irradiated with high-energy 56Fe ions. Cells were irradiated with graded doses of 56Fe ions (1 GeV/nucleon) accelerated with the Alternating Gradient Synchrotron at Brookhaven National Laboratory. The survival curves for cells plated 1 h after irradiation (immediate plating) showed little or no shoulder. However, the survival curves for cells plated 24 h after irradiation (delayed plating) had a small initial shoulder. The RBE for 56Fe ions compared to 137Cs gamma rays was 1.99 for immediate plating and 2.73 for delayed plating at the D10. The repair ratio (delayed plating/immediate plating) was 1.67 for 137Cs gamma rays and 1.22 for 56Fe ions. The dose-response curves for initially measured and residual chromatid fragments detected by the Calyculin A-mediated premature chromosome condensation technique showed a linear response. The results indicated that the induction frequency for initially measured fragments was the same for 137Cs gamma rays and 56Fe ions. On the other hand, approximately 85% of the fragments induced by 137Cs gamma rays had rejoined after 24 h of postirradiation incubation; the corresponding amount for 56Fe ions was 37%. Furthermore, the frequency of chromatid exchanges induced by gamma rays measured 24 h after irradiation was higher than that induced by 56Fe ions. No difference in the amount of chromatid damage induced by the two types of radiations was detected when assayed 1 h after irradiation. The results suggest that high-energy 56Fe ions induce a higher frequency of complex, unrepairable damage at both the cellular and chromosomal levels than 137Cs gamma rays in the target cells for radiation-induced lung cancers.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4199498','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4199498"><span>The Chromosomal Association of the Smc5/6 Complex Depends on Cohesion and Predicts the Level of Sister Chromatid Entanglement</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Jeppsson, Kristian; Carlborg, Kristian K.; Nakato, Ryuichiro; Berta, Davide G.; Lilienthal, Ingrid; Kanno, Takaharu; Lindqvist, Arne; Brink, Maartje C.; Dantuma, Nico P.; Katou, Yuki; Shirahige, Katsuhiko; Sjögren, Camilla</p>
<p>2014-01-01</p>
<p>The cohesin complex, which is essential for sister chromatid cohesion and chromosome segregation, also inhibits resolution of sister chromatid intertwinings (SCIs) by the topoisomerase Top2. The cohesin-related Smc5/6 complex (Smc5/6) instead accumulates on chromosomes after Top2 inactivation, known to lead to a buildup of unresolved SCIs. This suggests that cohesin can influence the chromosomal association of Smc5/6 via its role in SCI protection. Using high-resolution ChIP-sequencing, we show that the localization of budding yeast Smc5/6 to duplicated chromosomes indeed depends on sister chromatid cohesion in wild-type and top2-4 cells. Smc5/6 is found to be enriched at cohesin binding sites in the centromere-proximal regions in both cell types, but also along chromosome arms when replication has occurred under Top2-inhibiting conditions. Reactivation of Top2 after replication causes Smc5/6 to dissociate from chromosome arms, supporting the assumption that Smc5/6 associates with a Top2 substrate. It is also demonstrated that the amount of Smc5/6 on chromosomes positively correlates with the level of missegregation in top2-4, and that Smc5/6 promotes segregation of short chromosomes in the mutant. Altogether, this shows that the chromosomal localization of Smc5/6 predicts the presence of the chromatid segregation-inhibiting entities which accumulate in top2-4 mutated cells. These are most likely SCIs, and our results thus indicate that, at least when Top2 is inhibited, Smc5/6 facilitates their resolution. PMID:25329383</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25420521','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25420521"><span>Isolation and evaluation of cytogenetic effect of Brahmi saponins on cultured human lymphocytes exposed in vitro.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Kalachaveedu, Mangathayaru; Papacchan, Sunu; Sanyal, Sudip; Koshy, Teena; Telapolu, Srivani</p>
<p>2015-01-01</p>
<p>Major saponins of Brahmi (Bacopa monniera, Fam: Scrophulariaceae) - bacosides A and B - were isolated from the total methanol extract and characterised based on melting point, TLC, IR, (1)H NMR and (13)C NMR. They were evaluated for their in vitro cytogenetic effects on human peripheral blood lymphocytes by chromosomal aberration (CA) assay and sister chromatid exchange (SCE) assay. The frequency of chromatid type aberrations and reciprocal interchanges between sister chromatids in the treated cells was scored in comparison to the untreated control. At 30 μg/mL dose, bacoside A showed a statistically significant increase in the frequency of both CA and SCE and bacoside B showed an increase only in SCE. Our report of the genotoxicity of the saponins is significant in view of the reports of anticancer activity of Brahmi extracts.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1783675','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1783675"><span>Roles of the sister chromatid cohesion apparatus in gene expression, development, and human syndromes</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Dorsett, Dale</p>
<p>2006-01-01</p>
<p>The sister chromatid cohesion apparatus mediates physical pairing of duplicated chromosomes. This pairing is essential for appropriate distribution of chromosomes into the daughter cells upon cell division. Recent evidence shows that the cohesion apparatus, which is a significant structural component of chromosomes during interphase, also affects gene expression and development. The Cornelia de Lange (CdLS) and Roberts/SC phocomelia (RBS/SC) genetic syndromes in humans are caused by mutations affecting components of the cohesion apparatus. Studies in Drosophila suggest that effects on gene expression are most likely responsible for developmental alterations in CdLS. Effects on chromatid cohesion are apparent in RBS/SC syndrome, but data from yeast and Drosophila point to the likelihood that changes in expression of genes located in heterochromatin could contribute to the developmental deficits. PMID:16819604</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/391300-induction-sister-chromatid-exchange-presence-gadolinium-dtpa-its-reduction-dimethyl-sulfoxide','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/391300-induction-sister-chromatid-exchange-presence-gadolinium-dtpa-its-reduction-dimethyl-sulfoxide"><span>Induction of sister chromatid exchange in the presence of gadolinium-DTPA and its reduction by dimethyl sulfoxide</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Yamazaki, Etsuo; Fukuda, Hozumi; Shibuya, Hitoshi</p>
<p></p>
<p>The authors investigate the frequency of sister chromatid exchange (SCE) after the addition of gadolinium (Gd)-DTPA to venous blood samples. Venous blood was obtained from nonsmokers. Samples were incubated with Gd-DTPA alone or in combination with mitomycin C, cytarabine, and dimethyl sulfoxide (DMSO), and then evaluated for SCEs. The frequency of SCE increased with the concentration of Gd-DTPA and as each chemotherapeutic agent was added. Sister chromatid exchange frequencies were lower when the blood was treated with a combination of Gd-DTPA and DMSO compared with Gd-DTPA alone. The increase in frequency of SCE seen after the addition of Gd-DTPA wasmore » decreased by the addition of DMSO, indicating the production of hydroxyl radicals. The effect likely is dissociation-related. 14 refs., 6 tabs.« less</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/16309949','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/16309949"><span>Evaluation of genotoxic effects of Apitol (cymiazole hydrochloride) in vitro by measurement of sister chromatid exchange.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Stanimirovic, Zoran; Stevanovic, Jevrosima; Jovanovic, Slobodan; Andjelkovic, Marko</p>
<p>2005-12-30</p>
<p>Apitol, with cymiazole hydrochloride as the active ingredient, is used in bee-keeping against the ectoparasitic mite Varroa destructor. The preparation was evaluated for genotoxicity in cultured human peripheral blood lymphocytes. Sister chromatid exchange, the mitotic index and the cell proliferation index were determined for three experimental concentrations of Apitol (0.001, 0.01 and 0.1 mg/ml). All concentrations significantly (p < 0.001) increased the mitotic index (MI = 7.35+/-0.18%, 8.31+/-0.20% and 12.33+/-0.25%, respectively), the proliferative index (PI = 1.83+/-0.01, 1.84+/-0.01 and 1.88+/-0.02, respectively) and the frequency of sister chromatid exchange (SCE = 8.19+/-1.81, 8.78+/-1.80 and 13.46+/-1.88, respectively), suggesting that cymiazole hydrochloride has genotoxic potential.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3078076','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3078076"><span>Mitotic centromeric targeting of HP1 and its binding to Sgo1 are dispensable for sister-chromatid cohesion in human cells</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Kang, Jungseog; Chaudhary, Jaideep; Dong, Hui; Kim, Soonjoung; Brautigam, Chad A.; Yu, Hongtao</p>
<p>2011-01-01</p>
<p>Human Shugoshin 1 (Sgo1) protects centromeric sister-chromatid cohesion during prophase and prevents premature sister-chromatid separation. Heterochromatin protein 1 (HP1) has been proposed to protect centromeric sister-chromatid cohesion by directly targeting Sgo1 to centromeres in mitosis. Here we show that HP1α is targeted to mitotic centromeres by INCENP, a subunit of the chromosome passenger complex (CPC). Biochemical and structural studies show that both HP1–INCENP and HP1–Sgo1 interactions require the binding of the HP1 chromo shadow domain to PXVXL/I motifs in INCENP or Sgo1, suggesting that the INCENP-bound, centromeric HP1α is incapable of recruiting Sgo1. Consistently, a Sgo1 mutant deficient in HP1 binding is functional in centromeric cohesion protection and localizes normally to centromeres in mitosis. By contrast, INCENP or Sgo1 mutants deficient in HP1 binding fail to localize to centromeres in interphase. Therefore, our results suggest that HP1 binding by INCENP or Sgo1 is dispensable for centromeric cohesion protection during mitosis of human cells, but might regulate yet uncharacterized interphase functions of CPC or Sgo1 at the centromeres. PMID:21346195</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23681662','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23681662"><span>A CO-FISH assay to assess sister chromatid segregation patterns in mitosis of mouse embryonic stem cells.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Sauer, Stephan; Burkett, Sandra S; Lewandoski, Mark; Klar, Amar J S</p>
<p>2013-05-01</p>
<p>Sister chromatids contain identical DNA sequence but are chiral with respect to both their helical handedness and their replication history. Emerging evidence from various model organisms suggests that certain stem cells segregate sister chromatids nonrandomly to either maintain genome integrity or to bias cellular differentiation in asymmetric cell divisions. Conventional methods for tracing of old vs. newly synthesized DNA strands generally lack resolution for individual chromosomes and employ halogenated thymidine analogs with profound cytotoxic effects on rapidly dividing cells. Here, we present a modified chromosome orientation fluorescence in situ hybridization (CO-FISH) assay, where identification of individual chromosomes and their replication history is achieved in subsequent hybridization steps with chromosome-specific DNA probes and PNA telomere probes. Importantly, we tackle the issue of BrdU cytotoxicity and show that our method is compatible with normal mouse ES cell biology, unlike a recently published related protocol. Results from our CO-FISH assay show that mitotic segregation of mouse chromosome 7 is random in ES cells, which contrasts previously published results from our laboratory and settles a controversy. Our straightforward protocol represents a useful resource for future studies on chromatid segregation patterns of in vitro-cultured cells from distinct model organisms.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3791154','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3791154"><span>Strand-seq: a unifying tool for studies of chromosome segregation</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Falconer, Ester; Lansdorp, Peter M.</p>
<p>2013-01-01</p>
<p>Non random segregation of sister chromatids has been implicated to help specify daughter cell fate (the Silent Sister Hypothesis [1]) or to protect the genome of long-lived stem cells (the Immortal Strand Hypothesis [2]). The idea that sister chromatids are non-randomly segregated into specific daughter cells is only marginally supported by data in sporadic and often contradictory studies. As a result, the field has moved forward rather slowly. The advent of being able to directly label and differentiate sister chromatids in vivo using fluorescence in situ hybridization [3] was a significant advance for such studies. However, this approach is limited by the need for large tracks of unidirectional repeats on chromosomes and the reliance on quantitative imaging of fluorescent probes and rigorous statistical analysis to discern between the two competing hypotheses. A novel method called Strand-seq which uses next-generation sequencing to assay sister chromatid inheritance patterns independently for each chromosome [4] offers a comprehensive approach to test for non-random segregation. In addition Strand-seq enables studies on the deposition of chromatin marks in relation to DNA replication. This method is expected to help unify the field by testing previous claims of non-random segregation in an unbiased way in many model systems in vitro and in vivo. PMID:23665005</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11531014','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11531014"><span>A comparative study on cytogenetic and antineoplastic effects induced by two modified steroidal alkylating agents.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Papageorgiou, A; Tsavdaridis, D; Geromichalos, G D; Camoutsis, C; Karaberis, E; Mourelatos, D; Chrysogelou, E; Houvartas, S; Kotsis, A</p>
<p>2001-01-01</p>
<p>We investigated the effects of two newly synthesized steroidal derivatives of nitrogen mustard on sister chromatid exchange rates and on human lymphocyte proliferation kinetics. The compound 33-hydroxy-5alpha,22alpha-spirostan- 12-one-p-(N,N-bis(2-chloroethyl)amino)phenylacetate(1) was, on a molar basis, less effective in inducing sister chromatid exchange and suppressing cell proliferation rate indices than compound 3beta-hydroxy-12alpha-aza-C-homo-5alpha,22alpha-spirostan-12-one-p-(N,N-bis(2-chloroethyl)amino)phenylacetate(2). A correlation was observed between the magnitude of the sister chromatid exchange response and the depression of cell proliferation index. We also studied the effects of the aforementioned compounds on Lewis lung carcinoma. The order of the percent inhibition of tumor growth achieved by the compounds coincides with the order of the cytogenetic effects they induce.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/3165083','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/3165083"><span>Genes on chromosomes 1 and 4 in the mouse are associated with repair of radiation-induced chromatin damage.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Potter, M; Sanford, K K; Parshad, R; Tarone, R E; Price, F M; Mock, B; Huppi, K</p>
<p>1988-04-01</p>
<p>Early-passage skin fibroblasts from different inbred and congenic strains of mice were X-irradiated (1 Gy), and the number of chromatid breaks was determined at 2.0 h after irradiation. The cells from DBA/2N, C3H/HeN, STS/A, C57BL/6N, BALB/cJ, and AKR/N had 25 to 42 chromatid breaks per 100 metaphase cells (efficient repair phenotype). NZB/NJ had greater than 78 and BALB/cAn had 87 to 110 chromatid breaks per 100 cells (inefficient repair phenotype). Differences between BALB/cAn and BALB/c. DBA/2 congenic strains which carry less than 1% of the DBA/2 genome indicate that two genes, one on chromosome 1 linked to bcl-2-Pep-3 and the other on chromosome 4 closely linked to Fv-1, affect the efficiency with which the cells repair radiation-induced chromatin damage.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/10753184','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/10753184"><span>XPD polymorphisms: effects on DNA repair proficiency.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Lunn, R M; Helzlsouer, K J; Parshad, R; Umbach, D M; Harris, E L; Sanford, K K; Bell, D A</p>
<p>2000-04-01</p>
<p>XPD codes for a DNA helicase involved in transcription and nucleotide excision repair. Rare XPD mutations diminish nucleotide excision repair resulting in hypersensitivity to UV light and increased risk of skin cancer. Several polymorphisms in this gene have been identified but their impact on DNA repair is not known. We compared XPD genotypes at codons 312 and 751 with DNA repair proficiency in 31 women. XPD genotypes were measured by PCR-RFLP. DNA repair proficiency was assessed using a cytogenetic assay that detects X-ray induced chromatid aberrations (breaks and gaps). Chromatid aberrations were scored per 100 metaphase cells following incubation at 37 degrees C (1.5 h after irradiation) to allow for repair of DNA damage. Individuals with the Lys/Lys codon 751 XPD genotype had a higher number of chromatid aberrations (132/100 metaphase cells) than those having a 751Gln allele (34/100 metaphase cells). Individuals having greater than 60 chromatid breaks plus gaps were categorized as having sub-optimal repair. Possessing a Lys/Lys751 genotype increased the risk of sub-optimal DNA repair (odds ratio = 7.2, 95% confidence interval = 1.01-87.7). The Asp312Asn XPD polymorphism did not appear to affect DNA repair proficiency. These results suggest that the Lys751 (common) allele may alter the XPD protein product resulting in sub-optimal repair of X-ray-induced DNA damage.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23665005','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23665005"><span>Strand-seq: a unifying tool for studies of chromosome segregation.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Falconer, Ester; Lansdorp, Peter M</p>
<p>2013-01-01</p>
<p>Non random segregation of sister chromatids has been implicated to help specify daughter cell fate (the Silent Sister Hypothesis [1]) or to protect the genome of long-lived stem cells (the Immortal Strand Hypothesis [2]). The idea that sister chromatids are non-randomly segregated into specific daughter cells is only marginally supported by data in sporadic and often contradictory studies. As a result, the field has moved forward rather slowly. The advent of being able to directly label and differentiate sister chromatids in vivo using fluorescence in situ hybridization [3] was a significant advance for such studies. However, this approach is limited by the need for large tracks of unidirectional repeats on chromosomes and the reliance on quantitative imaging of fluorescent probes and rigorous statistical analysis to discern between the two competing hypotheses. A novel method called Strand-seq which uses next-generation sequencing to assay sister chromatid inheritance patterns independently for each chromosome [4] offers a comprehensive approach to test for non-random segregation. In addition Strand-seq enables studies on the deposition of chromatin marks in relation to DNA replication. This method is expected to help unify the field by testing previous claims of non-random segregation in an unbiased way in many model systems in vitro and in vivo. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20354861','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20354861"><span>Interaction between a pair of gypsy insulators or between heterologous gypsy and Wari insulators modulates Flp site-specific recombination in Drosophila melanogaster.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Krivega, Margarita; Savitskaya, Ekaterina; Krivega, Ivan; Karakozova, Marina; Parshikov, Aleksander; Golovnin, Anton; Georgiev, Pavel</p>
<p>2010-08-01</p>
<p>Chromatin insulators block the action of transcriptional enhancers when interposed between an enhancer and a promoter. An Flp technology was used to examine interactions between Drosophila gypsy and Wari insulators in somatic and germ cells. The gypsy insulator consists of 12 binding sites for the Su(Hw) protein, while the endogenous Wari insulator, located on the 3' side of the white gene, is independent from the Su(Hw) protein. Insertion of the gypsy but not Wari insulator between FRT sites strongly blocks recombination between Flp dimers bound to FRT sites located on the same chromatid (recombination in cis) or in sister chromatids (unequal recombination in trans). At the same time, the interaction between Wari and gypsy insulators regulates the efficiency of Flp-mediated recombination. Thus, insulators may have a role in controlling interactions between distantly located protein complexes (not only those involved in transcriptional gene regulation) on the same chromosome or on sister chromatids in somatic and germ cells. We have also found that the frequency of Flp-mediated recombination between FRT sites is strongly dependent on the relative orientation of gypsy insulators. Taken together, our results indicate that the interactions between insulators can be visualized by Flp technology and that insulators may be involved in blocking undesirable interactions between proteins at the two-chromatid phase of the cell cycle.</p>
</li>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29368476','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29368476"><span>[Inverted meiosis and its place in the evolution of sexual reproduction pathways].</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Bogdanov, Yu F</p>
<p>2016-05-01</p>
<p>Inverted meiosis is observed in plants (Cyperaceae and Juncaceae) and insects (Coccoidea, Aphididae) with holocentric chromosomes, the centromeres of which occupy from 70 to 90% of the metaphase chromosome length. In the first meiotic division (meiosis I), chiasmata are formed and rodlike bivalents orient equationally, and in anaphase I, sister chromatids segregate to the poles; the diploid chromosome number is maintained. Non-sister chromatids of homologous chromosomes remain in contact during interkinesis and prophase II and segregate in anaphase II, forming haploid chromosome sets. The segregation of sister chromatids in meiosis I was demonstrated by example of three plant species that were heterozygous for chromosomal rearrangements. In these species, sister chromatids, marked with rearrangement, segregated in anaphase I. Using fluorescent antibodies, it was demonstrated that meiotic recombination enzymes Spo11 and Rad5l, typical of canonical meiosis, functioned at the meiotic prophase I of pollen mother cells of Luzula elegance and Rhynchospora pubera. Moreover, antibodies to synaptonemal complexes proteins ASY1 and ZYP1 were visualized as filamentous structures, pointing to probable formation of synaptonemal complexes. In L. elegance, chiasmata are formed by means of chromatin threads containing satellite DNA. According to the hypothesis of the author of this review, equational division of sister chromatids at meiosis I in the organisms with inverted meiosis can be explained by the absence of specific meiotic proteins (shugoshins). These proteins are able to protect cohesins of holocentric centromeres from hydrolysis by separases at meiosis I, as occurs in the organisms with monocentric chromosomes and canonical meiosis. The basic type of inverted meiosis was described in Coccoidea and Aphididae males. In their females, the variants of parthenogenesis were also observed. Until now, the methods of molecular cytogenetics were not applied for the analysis of inverted meiosis in Coccoidea and Aphididae. Evolutionary, inverted meiosis is thought to have appeared secondarily as an adaptation of the molecular mechanisms of canonical meiosis to chromosome holocentrism.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/10827941','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/10827941"><span>Splitting the chromosome: cutting the ties that bind sister chromatids.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Nasmyth, K; Peters, J M; Uhlmann, F</p>
<p>2000-05-26</p>
<p>In eukaryotic cells, sister DNA molecules remain physically connected from their production at S phase until their separation during anaphase. This cohesion is essential for the separation of sister chromatids to opposite poles of the cell at mitosis. It also permits chromosome segregation to take place long after duplication has been completed. Recent work has identified a multisubunit complex called cohesin that is essential for connecting sisters. Proteolytic cleavage of one of cohesin's subunits may trigger sister separation at the onset of anaphase.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/6572531-enhanced-g2-chromatid-radiosensitivity-early-stage-neoplastic-transformation-human-epidermal-keratinocytes-culture','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/6572531-enhanced-g2-chromatid-radiosensitivity-early-stage-neoplastic-transformation-human-epidermal-keratinocytes-culture"><span>Enhanced G2 chromatid radiosensitivity, an early stage in the neoplastic transformation of human epidermal keratinocytes in culture</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Gantt, R.; Sanford, K.K.; Parshad, R.</p>
<p>1987-03-01</p>
<p>A deficiency in DNA repair, manifest as enhanced chromatid radiosensitivity during the G2 phase of the cell cycle, together with a proliferative stimulus such as that provided by active oncogenes may be necessary and sufficient for the malignant neoplastic transformation of human keratinocytes in culture. Normal epidermal keratinocytes established as continuous cell lines by transfection with pSV3-neo or infection with adeno 12-SV40 hybrid virus developed enhanced G2 chromatid radiosensitivity after 18 passages in culture. In contrast to cells from primary or secondary culture, these cells could be transformed to malignant neoplastic cells by infection with Kirsten murine sarcoma virus containingmore » the Ki-ras oncogene or in one line by the chemical carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine; both of these agents produced a marked proliferative response. Cytological heterogeneity and karyotypic instability characterized the cells during their progression to neoplasia. These results are interpreted in terms of a mechanism for neoplastic transformation.« less</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/5060660-sister-chromatid-exchanges-induced-inhaled-anesthetics','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/5060660-sister-chromatid-exchanges-induced-inhaled-anesthetics"><span>Sister chromatid exchanges induced by inhaled anesthetics</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>White,A.E.; Takehisa, S.; Eger II, E.I.</p>
<p>1970-05-01</p>
<p>There is sufficient evidence that anesthetics may cause cancer to justify a test of their carcinogenic potential. Baden et al., using the Ames test, a rapid and inexpensive genetic indicator of carcinogenicity, have shown that among currently used anesthetics fluorxene alone caused bacterial mutations. The authors used the sister chromatid exchange (SCE) technique, another rapid assay of mutagenic-carcinogenic potential. The frequency of sister chromatid exchanges in Chinese hamster ovary cells increases when the cell cultures are exposed to mutagen-carcinogens, particulary in the presence of a metabolic activating system. With this test system a one-hour exposure to 1 MAC nitrous oxide,more » diethyl ether, trichloroethylene, halothane, enflurane, isoflurane, methoxyflurane, or chloroform did not increase SCE values. Divinyl ether, fluroxene and ethyl vinyl ether increased SCE values in the same circumstances. Results of this study of mammalian cells suggest that no currently used anesthetic is a mutagen-carcinogen. The results also suggest that anesthetics containing a vinyl moiety may be mutagen-carcinogens.« less</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/6769065-genes-chromosomes-mouse-associated-repair-radiation-induced-chromatin-damage','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/6769065-genes-chromosomes-mouse-associated-repair-radiation-induced-chromatin-damage"><span>Genes on chromosomes 1 and 4 in the mouse are associated with repair of radiation-induced chromatin damage</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Potter, M.; Sanford, K.K.; Parshad, R.</p>
<p></p>
<p>Early-passage skin fibroblasts from different inbred and congenic strains of mice were X-irradiated (1 Gy), and the number of chromatid breaks was determined at 2.0 h after irradiation. The cells from DBA/2N, C3H/HeN, STS/A, C57BL/6N, BALB/cJ, and AKR/N had 25 to 42 chromatid breaks per 100 metaphase cells (efficient repair phenotype). NZB/NJ had greater than 78 and BALB/cAn had 87 to 110 chromatid breaks per 100 cells (inefficient repair phenotype). Differences between BALB/cAn and BALB/c. DBA/2 congenic strains which carry less than 1% of the DBA/2 genome indicate that two genes, one on chromosome 1 linked to bcl-2-Pep-3 and themore » other on chromosome 4 closely linked to Fv-1, affect the efficiency with which the cells repair radiation-induced chromatin damage.« less</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2224871','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2224871"><span>The Rejoining Time of Chromatid Breaks Induced by Gamma Radiation in Vicia faba Root Tips at 3 °C</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Savage, J. R. K.; Neary, G. J.; Evans, H. J.</p>
<p>1960-01-01</p>
<p>The observation was made previously that the reduction in radiosensitivity in Vicia faba (as measured by postirradiation root growth) by prolonging the exposure time from about 10 minutes to 24 hours is much less marked at 3°C. than at 19°C. If chromosome damage is mainly responsible for the reduced root growth, this observation might be explained by a smaller drop in the "two-hit" aberration component, resulting from an increased time for which breaks are available for rejoining at 3°C. This hypothesis was tested by comparing chromatid aberration frequencies in root meristem cells produced by 105 rads of 60Co γ rays, given at dose rates of 19.4 and 0.073 rads per minute. Beans were maintained in aerated water at 2°C. prior to and during irradiation, and at this temperature the rate of development of cells was such that the two different exposure times both occupied a period during which the cell sensitivity was approximately constant. Immediately subsequent to irradiation, the roots were returned to 19°C. and examined cytologically. All chromatid aberrations were less frequent after low dose rate treatment, but only the chromatid interchange reduction was significant. The average time for which breaks are available for reunion, calculated from Lea's G function, was found to be 12 hours (95 per cent C.L. 6 to 24 hours). PMID:14442001</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1128680','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1128680"><span>DNA single strand breakage, DNA adducts, and sister chromatid exchange in lymphocytes and phenanthrene and pyrene metabolites in urine of coke oven workers.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Popp, W; Vahrenholz, C; Schell, C; Grimmer, G; Dettbarn, G; Kraus, R; Brauksiepe, A; Schmeling, B; Gutzeit, T; von Bülow, J; Norpoth, K</p>
<p>1997-01-01</p>
<p>OBJECTIVES: To investigate the specificity of biological monitoring variables (excretion of phenanthrene and pyrene metabolites in urine) and the usefulness of some biomarkers of effect (alkaline filter elution, 32P postlabelling assay, measurement of sister chromatid exchange) in workers exposed to polycyclic aromatic hydrocarbons (PAHs). METHODS: 29 coke oven workers and a standardised control group were investigated for frequencies of DNA single strand breakage, DNA protein cross links (alkaline filter elution assay), sister chromatid exchange, and DNA adducts (32P postlabelling assay) in lymphocytes. Phenanthrene and pyrene metabolites were measured in 24 hour urine samples. 19 different PAHs (including benzo(a)pyrene, pyrene, and phenanthrene) were measured at the workplace by personal air monitoring. The GSTT1 activity in erythrocytes and lymphocyte subpopulations in blood was also measured. RESULTS: Concentrations of phenanthrene, pyrene, and benzo(a)pyrene in air correlated well with the concentration of total PAHs in air; they could be used for comparisons of different workplaces if the emission compositions were known. The measurement of phenanthrene metabolites in urine proved to be a better biological monitoring variable than the measurement of 1-hydroxypyrene. Significantly more DNA strand breaks in lymphocytes of coke oven workers were found (alkaline filter elution assay); the DNA adduct rate was not significantly increased in workers, but correlated with exposure to PAHs in a semiquantitative manner. The number of sister chromatid exchanges was lower in coke oven workers but this was not significant; thus counting sister chromatid exchanges was not a good variable for biomonitoring of coke oven workers. Also, indications for immunotoxic influences (changes in lymphocyte subpopulations) were found. CONCLUSIONS: The measurement of phenanthrene metabolites in urine seems to be a better biological monitoring variable for exposure to PAHs than measurement of hydroxypyrene. The alkaline filter elution assay proved to be the most sensitive biomarker for genotoxic damage, whereas the postlabelling assay was the only one with some specificity for DNA alterations caused by known compounds. PMID:9155778</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29276124','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29276124"><span>Sex- and Gamete-Specific Patterns of X Chromosome Segregation in a Trioecious Nematode.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Tandonnet, Sophie; Farrell, Maureen C; Koutsovoulos, Georgios D; Blaxter, Mark L; Parihar, Manish; Sadler, Penny L; Shakes, Diane C; Pires-daSilva, Andre</p>
<p>2018-01-08</p>
<p>Three key steps in meiosis allow diploid organisms to produce haploid gametes: (1) homologous chromosomes (homologs) pair and undergo crossovers; (2) homologs segregate to opposite poles; and (3) sister chromatids segregate to opposite poles. The XX/XO sex determination system found in many nematodes [1] facilitates the study of meiosis because variation is easily recognized [2-4]. Here we show that meiotic segregation of X chromosomes in the trioecious nematode Auanema rhodensis [5] varies according to sex (hermaphrodite, female, or male) and type of gametogenesis (oogenesis or spermatogenesis). In this species, XO males exclusively produce X-bearing sperm [6, 7]. The unpaired X precociously separates into sister chromatids, which co-segregate with the autosome set to generate a functional haplo-X sperm. The other set of autosomes is discarded into a residual body. Here we explore the X chromosome behavior in female and hermaphrodite meioses. Whereas X chromosomes segregate following the canonical pattern during XX female oogenesis to yield haplo-X oocytes, during XX hermaphrodite oogenesis they segregate to the first polar body to yield nullo-X oocytes. Thus, crosses between XX hermaphrodites and males yield exclusively male progeny. During hermaphrodite spermatogenesis, the sister chromatids of the X chromosomes separate during meiosis I, and homologous X chromatids segregate to the functional sperm to create diplo-X sperm. Given these intra-species, intra-individual, and intra-gametogenesis variations in the meiotic program, A. rhodensis is an ideal model for studying the plasticity of meiosis and how it can be modulated. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/6488477','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/6488477"><span>Increased incidence of chromosomal aberrations in peripheral lymphocytes of retired nickel workers.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Waksvik, H; Boysen, M; Høgetveit, A C</p>
<p>1984-11-01</p>
<p>Chromosomal aberrations and sister chromatid exchanges were analysed in the peripheral lymphocytes of nine retired nickel refinery workers 4-15 years after the retirement and compared with 11 matched non-nickel exposed controls. None of the controls had previous occupations with known relation to induction of chromosomal aberrations nor sister chromatid exchanges. The groups were equal as to socioeconomic status and environmental factors other than the occupational ones, which could influence the chromosome parameters, were to the largest possible extent excluded. The nickel workers' previous occupational employment involved exposure to inhalation of furnace dust of Ni3S2 and NiO or aerosols of NiCl2 and NiSO4. The concentration of nickel in the working atmospheres has been higher than 1.0 mg/m3 air and the exposure time more than 25 years. The retired nickel workers showed an increased incidence of breaks (p less than 0.001) and gaps (p less than 0.05) but no difference in the incidence of sister chromatid exchanges when compared with the controls.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27889450','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27889450"><span>RPA Mediates Recruitment of MRX to Forks and Double-Strand Breaks to Hold Sister Chromatids Together.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Seeber, Andrew; Hegnauer, Anna Maria; Hustedt, Nicole; Deshpande, Ishan; Poli, Jérôme; Eglinger, Jan; Pasero, Philippe; Gut, Heinz; Shinohara, Miki; Hopfner, Karl-Peter; Shimada, Kenji; Gasser, Susan M</p>
<p>2016-12-01</p>
<p>The Mre11-Rad50-Xrs2 (MRX) complex is related to SMC complexes that form rings capable of holding two distinct DNA strands together. MRX functions at stalled replication forks and double-strand breaks (DSBs). A mutation in the N-terminal OB fold of the 70 kDa subunit of yeast replication protein A, rfa1-t11, abrogates MRX recruitment to both types of DNA damage. The rfa1 mutation is functionally epistatic with loss of any of the MRX subunits for survival of replication fork stress or DSB recovery, although it does not compromise end-resection. High-resolution imaging shows that either the rfa1-t11 or the rad50Δ mutation lets stalled replication forks collapse and allows the separation not only of opposing ends but of sister chromatids at breaks. Given that cohesin loss does not provoke visible sister separation as long as the RPA-MRX contacts are intact, we conclude that MRX also serves as a structural linchpin holding sister chromatids together at breaks. Copyright © 2016 Elsevier Inc. All rights reserved.</p>
</li>
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<ol class="result-class" start="81">
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25975148','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25975148"><span>[Structural and functional organization of centromeres in plant chromosomes].</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Silkova, O G; Loginova, D B</p>
<p>2014-12-01</p>
<p>The centromere is a specific chromosomal locus that forms the protein complex and kinetochore, maintains sister chromatid cohesion, controls chromosome attachment to the spindle, and coordinates chromosome movement during mitosis and meiosis. Defective centromere assembly or its dysfunction causes cell cycle arrest, structural abnormalities of the chromosomes, and aneuploidy. This review collects the data on the structure, functions, and epigenetic modification of centromeric chromatin, the structure and functions of the kinetochore, and sister chromatid cohesion. Taken together, these data provide insight into the specific architecture and functioning of the centromere during chromosome division and segregation in plants.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29186203','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29186203"><span>Chl1 DNA helicase and Scc2 function in chromosome condensation through cohesin deposition.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Shen, Donglai; Skibbens, Robert V</p>
<p>2017-01-01</p>
<p>Chl1 DNA helicase promotes sister chromatid cohesion and associates with both the cohesion establishment acetyltransferase Eco1/Ctf7 and the DNA polymerase processivity factor PCNA that supports Eco1/Ctf7 function. Mutation in CHL1 results in precocious sister chromatid separation and cell aneuploidy, defects that arise through reduced levels of chromatin-bound cohesins which normally tether together sister chromatids (trans tethering). Mutation of Chl1 family members (BACH1/BRIP/FANCJ and DDX11/ChlR1) also exhibit genotoxic sensitivities, consistent with a role for Chl1 in trans tethering which is required for efficient DNA repair. Chl1 promotes the recruitment of Scc2 to DNA which is required for cohesin deposition onto DNA. There is limited evidence, however, that Scc2 also directs the deposition onto DNA of condensins which promote tethering in cis (intramolecular DNA links). Here, we test the ability of Chl1 to promote cis tethering and the role of both Chl1 and Scc2 to promote condensin recruitment to DNA. The results reveal that chl1 mutant cells exhibit significant condensation defects both within the rDNA locus and genome-wide. Importantly, chl1 mutant cell condensation defects do not result from reduced chromatin binding of condensin, but instead through reduced chromatin binding of cohesin. We tested scc2-4 mutant cells and similarly found no evidence of reduced condensin recruitment to chromatin. Consistent with a role for Scc2 specifically in cohesin deposition, scc2-4 mutant cell condensation defects are irreversible. We thus term Chl1 a novel regulator of both chromatin condensation and sister chromatid cohesion through cohesin-based mechanisms. These results reveal an exciting interface between DNA structure and the highly conserved cohesin complex.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5706694','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5706694"><span>Chl1 DNA helicase and Scc2 function in chromosome condensation through cohesin deposition</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Shen, Donglai</p>
<p>2017-01-01</p>
<p>Chl1 DNA helicase promotes sister chromatid cohesion and associates with both the cohesion establishment acetyltransferase Eco1/Ctf7 and the DNA polymerase processivity factor PCNA that supports Eco1/Ctf7 function. Mutation in CHL1 results in precocious sister chromatid separation and cell aneuploidy, defects that arise through reduced levels of chromatin-bound cohesins which normally tether together sister chromatids (trans tethering). Mutation of Chl1 family members (BACH1/BRIP/FANCJ and DDX11/ChlR1) also exhibit genotoxic sensitivities, consistent with a role for Chl1 in trans tethering which is required for efficient DNA repair. Chl1 promotes the recruitment of Scc2 to DNA which is required for cohesin deposition onto DNA. There is limited evidence, however, that Scc2 also directs the deposition onto DNA of condensins which promote tethering in cis (intramolecular DNA links). Here, we test the ability of Chl1 to promote cis tethering and the role of both Chl1 and Scc2 to promote condensin recruitment to DNA. The results reveal that chl1 mutant cells exhibit significant condensation defects both within the rDNA locus and genome-wide. Importantly, chl1 mutant cell condensation defects do not result from reduced chromatin binding of condensin, but instead through reduced chromatin binding of cohesin. We tested scc2-4 mutant cells and similarly found no evidence of reduced condensin recruitment to chromatin. Consistent with a role for Scc2 specifically in cohesin deposition, scc2-4 mutant cell condensation defects are irreversible. We thus term Chl1 a novel regulator of both chromatin condensation and sister chromatid cohesion through cohesin-based mechanisms. These results reveal an exciting interface between DNA structure and the highly conserved cohesin complex. PMID:29186203</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/12787819','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/12787819"><span>Sister chromatid exchanges and micronuclei analysis in lymphocytes of men exposed to simazine through drinking water.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Suárez, Susanna; Rubio, Arantxa; Sueiro, Rosa Ana; Garrido, Joaquín</p>
<p>2003-06-06</p>
<p>In some cities of the autonomous community of Extremadura (south-west of Spain), levels of simazine from 10 to 30 ppm were detected in tap water. To analyse the possible effect of this herbicide, two biomarkers, sister chromatid exchanges (SCE) and micronuclei (MN), were used in peripheral blood lymphocytes from males exposed to simazine through drinking water. SCE and MN analysis failed to detect any statistically significant increase in the people exposed to simazine when compared with the controls. With respect to high frequency cells (HFC), a statistically significant difference was detected between exposed and control groups.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=20040087649&hterms=ito&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D50%26Ntt%3Dito','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=20040087649&hterms=ito&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D50%26Ntt%3Dito"><span>Induction of chromatin damage and distribution of isochromatid breaks in human fibroblast cells exposed to heavy ions</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p>
<p>Kawata, Tetsuya; Ito, Hisao; Motoori, Ken; Ueda, Takuya; Shigematsu, Naoyuki; Furusawa, Yoshiya; Durante, Marco; George, Kerry; Wu, Honglu; Cucinotta, Francis A.</p>
<p>2002-01-01</p>
<p>The frequency of chromatid breaks and the distribution of isochromatid breaks were measured in G2-phase normal human fibroblasts prematurely condensed a short time after exposure to low- or high-LET radiations. The average number of isochromatid breaks from a single particle traversal increased with increasing LET values, while the average number of chromatid-type breaks appeared to reach a plateau. The distribution of isochromatid breaks after high-LET iron particles exposure was overdispersed compared to gamma-rays, indicating that a single iron particle traversal through a cell nucleus can produce multiple isochromatid breaks.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/12793753','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/12793753"><span>Induction of chromatin damage and distribution of isochromatid breaks in human fibroblast cells exposed to heavy ions.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Kawata, Tetsuya; Ito, Hisao; Motoori, Ken; Ueda, Takuya; Shigematsu, Naoyuki; Furusawa, Yoshiya; Durante, Marco; George, Kerry; Wu, Honglu; Cucinotta, Francis A</p>
<p>2002-12-01</p>
<p>The frequency of chromatid breaks and the distribution of isochromatid breaks were measured in G2-phase normal human fibroblasts prematurely condensed a short time after exposure to low- or high-LET radiations. The average number of isochromatid breaks from a single particle traversal increased with increasing LET values, while the average number of chromatid-type breaks appeared to reach a plateau. The distribution of isochromatid breaks after high-LET iron particles exposure was overdispersed compared to gamma-rays, indicating that a single iron particle traversal through a cell nucleus can produce multiple isochromatid breaks.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/6842348-ultraviolet-induced-sister-chromatid-exchanges-cells-normal-brdurd-substituted-dna-influence-intercalating-substances-cysteine','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/6842348-ultraviolet-induced-sister-chromatid-exchanges-cells-normal-brdurd-substituted-dna-influence-intercalating-substances-cysteine"><span>Ultraviolet-induced sister chromatid exchanges in V-79 cells with normal and BrdUrd-substituted DNA and the influence of intercalating substances and cysteine</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Speit, G.; Mehnert, K.; Wolf, M.</p>
<p>1982-06-01</p>
<p>The influence of intercalating substances (proflavine, ethidium bromide) and of an SH compound (L-cysteine) on uv-induced sister chromatid exchanges (SCEs) was investigated in V-79 cells with normal and BrdUrd-substituted DNA. The results are discussed in relation to the primary damages leading to SCE induction produced by uv irradiation. The data indicate that neither the pyrimidine dimers nor DNA single-strand breaks are the primary cause of SCE induction, and that the damages leading to SCEs by uv irradiation differ from those which cause chromosome aberrations.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21743463','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21743463"><span>Cleavage of cohesin rings coordinates the separation of centrioles and chromatids.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Schöckel, Laura; Möckel, Martin; Mayer, Bernd; Boos, Dominik; Stemmann, Olaf</p>
<p>2011-07-10</p>
<p>Cohesin pairs sister chromatids by forming a tripartite Scc1-Smc1-Smc3 ring around them. In mitosis, cohesin is removed from chromosome arms by the phosphorylation-dependent prophase pathway. Centromeric cohesin is protected by shugoshin 1 and protein phosphatase 2A (Sgo1-PP2A) and opened only in anaphase by separase-dependent cleavage of Scc1 (refs 4-6). Following chromosome segregation, centrioles loosen their tight orthogonal arrangement, which licenses later centrosome duplication in S phase. Although a role of separase in centriole disengagement has been reported, the molecular details of this process remain enigmatic. Here, we identify cohesin as a centriole-engagement factor. Both premature sister-chromatid separation and centriole disengagement are induced by ectopic activation of separase or depletion of Sgo1. These unscheduled events are suppressed by expression of non-cleavable Scc1 or inhibition of the prophase pathway. When endogenous Scc1 is replaced by artificially cleavable Scc1, the corresponding site-specific protease triggers centriole disengagement. Separation of centrioles can alternatively be induced by ectopic cleavage of an engineered Smc3. Thus, the chromosome and centrosome cycles exhibit extensive parallels and are coordinated with each other by dual use of the cohesin ring complex.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20551608','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20551608"><span>Behavior of centromeres in univalents and centric misdivision in wheat.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Lukaszewski, A J</p>
<p>2010-07-01</p>
<p>Centromeres are responsible for the proper behavior of chromosomes in cell divisions. In meiosis the process is more complicated than in mitosis, as each chromosome in a bivalent has 2 sister centromeres and their behavior has to be strictly coordinated. Here, the behavior of sister centromeres in univalents in wheat is examined, showing that by metaphase I they often lose their coordination. This loss accelerates with the progression of anaphase I, leading to stable bipolar attachment and frequent separation of sister chromatids or to misdivision. Depending on the orientation of a univalent and its sister centromeres, misdivision may occur across the centromere region or across the pericentric chromatin. Chromosome fragments consisting of only the centromere region did not survive to the next generation. Midget chromosomes composed of the centromeres and parts of the pericentric chromatin did survive, but their transmission rates were low and appeared related to the amount of pericentric chromatin, probably because only the pericentric chromatin provides sister chromatid cohesion. As the cohesion of sister chromatids appears to be a function of the proximity to the kinetochore region, the definition of the centromere need not include pericentric regions. Copyright 2010 S. Karger AG, Basel.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3113765','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3113765"><span>Scc2 regulates gene expression by recruiting cohesin to the chromosome as a transcriptional activator during yeast meiosis</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Lin, Weiqiang; Jin, Hui; Liu, Xiuwen; Hampton, Kristin; Yu, Hong-Guo</p>
<p>2011-01-01</p>
<p>To tether sister chromatids, a protein-loading complex, including Scc2, recruits cohesin to the chromosome at discrete loci. Cohesin facilitates the formation of a higher-order chromosome structure that could also influence gene expression. How cohesin directly regulates transcription remains to be further elucidated. We report that in budding yeast Scc2 is required for sister-chromatid cohesion during meiosis for two reasons. First, Scc2 is required for activating the expression of REC8, which encodes a meiosis-specific cohesin subunit; second, Scc2 is necessary for recruiting meiotic cohesin to the chromosome to generate sister-chromatid cohesion. Using a heterologous reporter assay, we have found that Scc2 increases the activity of its target promoters by recruiting cohesin to establish an upstream cohesin-associated region in a position-dependent manner. Rec8-associated meiotic cohesin is required for the full activation of the REC8 promoter, revealing that cohesin has a positive feedback on transcriptional regulation. Finally, we provide evidence that chromosomal binding of cohesin is sufficient for target-gene activation during meiosis. Our data support a noncanonical role for cohesin as a transcriptional activator during cell differentiation. PMID:21508318</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/servlets/purl/873174','DOE-PATENT-XML'); return false;" href="https://www.osti.gov/servlets/purl/873174"><span>Determining orientation and direction of DNA sequences</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/doepatents">DOEpatents</a></p>
<p>Goodwin, Edwin H.; Meyne, Julianne</p>
<p>2000-01-01</p>
<p>Determining orientation and direction of DNA sequences. A method by which fluorescence in situ hybridization can be made strand specific is described. Cell cultures are grown in a medium containing a halogenated nucleotide. The analog is partially incorporated in one DNA strand of each chromatid. This substitution takes place in opposite strands of the two sister chromatids. After staining with the fluorescent DNA-binding dye Hoechst 33258, cells are exposed to long-wavelength ultraviolet light which results in numerous strand nicks. These nicks enable the substituted strand to be denatured and solubilized by heat, treatment with high or low pH aqueous solutions, or by immersing the strands in 2.times.SSC (0.3M NaCl+0.03M sodium citrate), to name three procedures. It is unnecessary to enzymatically digest the strands using Exo III or another exonuclease in order to excise and solubilize nucleotides starting at the sites of the nicks. The denaturing/solubilizing process removes most of the substituted strand while leaving the prereplication strand largely intact. Hybridization of a single-stranded probe of a tandem repeat arranged in a head-to-tail orientation will result in hybridization only to the chromatid with the complementary strand present.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11748978','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11748978"><span>Sister chromatid exchange rate and alkaline comet assay scores in patients with ovarian cancer.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Baltaci, Volkan; Kayikçioğlu, Fulya; Alpas, Idil; Zeyneloğlu, Hulusi; Haberal, Ali</p>
<p>2002-01-01</p>
<p>Sister chromatid exchange (SCE) frequencies were studied in patients with different types of ovarian malignancies and in healthy volunteers. The level of DNA damage in patients with ovarian malignancy and control subjects has also been studied by alkaline single cell gel electrophoresis (SCGE), also known as the comet assay. Peripheral blood was collected from 30 patients after histological confirmation of malignancy and 20 healthy female volunteers. The cells were evaluated according to their grade of damage. We found that the sister chromatid exchange frequencies of cancer cases were significantly greater than that of controls (P < 0.001). The frequency of exchange in chromosomal groups A, B, and C, which include chromosomes 1-12, was higher than that of the other chromosomal groups in both groups. Comparison of the results of the alkaline comet assay in patient and control subjects showed a significant difference in the number of damaged cells. The frequency of limited migrated and extensive migrated cells in the women with ovarian malignancies was higher than that of control women (P < 0.001). SCE and SCGE can be used successfully to monitor DNA damage in women with ovarian cancer.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/7050066-vitro-effect-fenthion-human-lymphocytes','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/7050066-vitro-effect-fenthion-human-lymphocytes"><span>In vitro effect of fenthion on human lymphocytes</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Rani, M.V.U.; Rao, M.S.</p>
<p>1991-08-01</p>
<p>Fenthion is an organophosphorus insecticide which is extensively used in control of leaf hoppers, cutworms, mites on vegetable crops. It has been reported that organophosphorus pesticides cause a significant increase in sister chromatid exchanges in mammalian cell lines. A significant increase of chromosomal aberrations has been reported in rural population exposed to pesticides. Organosphosphorus pesticides malathion, diazinon, dimethoate, phosdrin and dursban induced sister chromatid exchanges in human lymphoid cells. Exchange type of aberration has been reported in fluoriculturist who were exposed to organophosphorus, organochlorine pesticides. In the present investigation an attempt has been made to evaluate the cytogenetic effect ofmore » fenthion in human lymphocyte cultures in vitro.« less</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/3442830','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/3442830"><span>Indirect intergenic suppression of a radiosensitive mutant of Sordaria macrospora defective in sister-chromatid cohesiveness.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Huynh, A D; Leblon, G; Zickler, D</p>
<p>1986-01-01</p>
<p>Six ultra violet (UV) mutageneses were performed on the spo76 UV-sensitive mutant of Sordaria macrospora. Spo76 shows an early centromere cleavage associated with an arrest at the first meiotic division and therefore does not form ascospores. Moreover, it exhibits altered pairing structure (synaptonemal complex), revealing a defect in the sister-chromatid cohesiveness. From 37 revertants which partially restored sporulation, 34 extragenic suppressors of spo76 were isolated. All suppressors are altered in chromosomal pairing but, unlike spo76, show a wild type centromere cleavage. The 34 suppressors were assigned to six different genes and mapped. Only one of the suppressor genes is involved in repair functions.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4643289','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4643289"><span>Titanium Dioxide Nanoparticles are not Cytotoxic or Clastogenic in Human Skin Cells</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Browning, Cynthia L; The, Therry; Mason, Michael D; Wise, John Pierce</p>
<p>2015-01-01</p>
<p>The application of nanoparticle technology is rapidly expanding. The reduced dimensionality of nanoparticles can give rise to changes in chemical and physical properties, often resulting in altered toxicity. People are exposed dermally to titanium dioxide (TiO2) nanoparticles in industrial and residential settings. The general public is increasingly exposed to these nanoparticles as their use in cosmetics, sunscreens and lotions expands. The toxicity of TiO2 nanoparticles towards human skin cells is unclear and understudied. We used a human skin fibroblast cell line to investigate the cytotoxicity and clastogenicity of TiO2 nanoparticles after 24 h exposure. In a clonogenic survival assay, treatments of 10, 50 and 100 μg/cm2 induced 97.8, 88.8 and 84.7% relative survival, respectively. Clastogenicity was assessed using a chromosomal aberration assay in order to determine whether TiO2 nanoparticles induced serious forms of DNA damage such as chromatid breaks, isochromatid lesions or chromatid exchanges. Treatments of 0, 10, 50 and 100 μg/cm2 induced 3.3, 3.0, 3.0 and 2.7% metaphases with damage, respectively. No isochromatid lesions or chromatid exchanges were detected. These data show that TiO2 nanoparticles are not cytotoxic or clastogenic to human skin cells. PMID:26568896</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26568896','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26568896"><span>Titanium Dioxide Nanoparticles are not Cytotoxic or Clastogenic in Human Skin Cells.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Browning, Cynthia L; The, Therry; Mason, Michael D; Wise, John Pierce</p>
<p>2014-11-01</p>
<p>The application of nanoparticle technology is rapidly expanding. The reduced dimensionality of nanoparticles can give rise to changes in chemical and physical properties, often resulting in altered toxicity. People are exposed dermally to titanium dioxide (TiO 2 ) nanoparticles in industrial and residential settings. The general public is increasingly exposed to these nanoparticles as their use in cosmetics, sunscreens and lotions expands. The toxicity of TiO 2 nanoparticles towards human skin cells is unclear and understudied. We used a human skin fibroblast cell line to investigate the cytotoxicity and clastogenicity of TiO 2 nanoparticles after 24 h exposure. In a clonogenic survival assay, treatments of 10, 50 and 100 μg/cm 2 induced 97.8, 88.8 and 84.7% relative survival, respectively. Clastogenicity was assessed using a chromosomal aberration assay in order to determine whether TiO 2 nanoparticles induced serious forms of DNA damage such as chromatid breaks, isochromatid lesions or chromatid exchanges. Treatments of 0, 10, 50 and 100 μg/cm 2 induced 3.3, 3.0, 3.0 and 2.7% metaphases with damage, respectively. No isochromatid lesions or chromatid exchanges were detected. These data show that TiO 2 nanoparticles are not cytotoxic or clastogenic to human skin cells.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3715423','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3715423"><span>The Cohesion Protein SOLO Associates with SMC1 and Is Required for Synapsis, Recombination, Homolog Bias and Cohesion and Pairing of Centromeres in Drosophila Meiosis</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Yan, Rihui; McKee, Bruce D.</p>
<p>2013-01-01</p>
<p>Cohesion between sister chromatids is mediated by cohesin and is essential for proper meiotic segregation of both sister chromatids and homologs. solo encodes a Drosophila meiosis-specific cohesion protein with no apparent sequence homology to cohesins that is required in male meiosis for centromere cohesion, proper orientation of sister centromeres and centromere enrichment of the cohesin subunit SMC1. In this study, we show that solo is involved in multiple aspects of meiosis in female Drosophila. Null mutations in solo caused the following phenotypes: 1) high frequencies of homolog and sister chromatid nondisjunction (NDJ) and sharply reduced frequencies of homolog exchange; 2) reduced transmission of a ring-X chromosome, an indicator of elevated frequencies of sister chromatid exchange (SCE); 3) premature loss of centromere pairing and cohesion during prophase I, as indicated by elevated foci counts of the centromere protein CID; 4) instability of the lateral elements (LE)s and central regions of synaptonemal complexes (SCs), as indicated by fragmented and spotty staining of the chromosome core/LE component SMC1 and the transverse filament protein C(3)G, respectively, at all stages of pachytene. SOLO and SMC1 are both enriched on centromeres throughout prophase I, co-align along the lateral elements of SCs and reciprocally co-immunoprecipitate from ovarian protein extracts. Our studies demonstrate that SOLO is closely associated with meiotic cohesin and required both for enrichment of cohesin on centromeres and stable assembly of cohesin into chromosome cores. These events underlie and are required for stable cohesion of centromeres, synapsis of homologous chromosomes, and a recombination mechanism that suppresses SCE to preferentially generate homolog crossovers (homolog bias). We propose that SOLO is a subunit of a specialized meiotic cohesin complex that mediates both centromeric and axial arm cohesion and promotes homolog bias as a component of chromosome cores. PMID:23874232</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23874232','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23874232"><span>The cohesion protein SOLO associates with SMC1 and is required for synapsis, recombination, homolog bias and cohesion and pairing of centromeres in Drosophila Meiosis.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Yan, Rihui; McKee, Bruce D</p>
<p>2013-01-01</p>
<p>Cohesion between sister chromatids is mediated by cohesin and is essential for proper meiotic segregation of both sister chromatids and homologs. solo encodes a Drosophila meiosis-specific cohesion protein with no apparent sequence homology to cohesins that is required in male meiosis for centromere cohesion, proper orientation of sister centromeres and centromere enrichment of the cohesin subunit SMC1. In this study, we show that solo is involved in multiple aspects of meiosis in female Drosophila. Null mutations in solo caused the following phenotypes: 1) high frequencies of homolog and sister chromatid nondisjunction (NDJ) and sharply reduced frequencies of homolog exchange; 2) reduced transmission of a ring-X chromosome, an indicator of elevated frequencies of sister chromatid exchange (SCE); 3) premature loss of centromere pairing and cohesion during prophase I, as indicated by elevated foci counts of the centromere protein CID; 4) instability of the lateral elements (LE)s and central regions of synaptonemal complexes (SCs), as indicated by fragmented and spotty staining of the chromosome core/LE component SMC1 and the transverse filament protein C(3)G, respectively, at all stages of pachytene. SOLO and SMC1 are both enriched on centromeres throughout prophase I, co-align along the lateral elements of SCs and reciprocally co-immunoprecipitate from ovarian protein extracts. Our studies demonstrate that SOLO is closely associated with meiotic cohesin and required both for enrichment of cohesin on centromeres and stable assembly of cohesin into chromosome cores. These events underlie and are required for stable cohesion of centromeres, synapsis of homologous chromosomes, and a recombination mechanism that suppresses SCE to preferentially generate homolog crossovers (homolog bias). We propose that SOLO is a subunit of a specialized meiotic cohesin complex that mediates both centromeric and axial arm cohesion and promotes homolog bias as a component of chromosome cores.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2013-title40-vol17/pdf/CFR-2013-title40-vol17-sec79-53.pdf','CFR2013'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2013-title40-vol17/pdf/CFR-2013-title40-vol17-sec79-53.pdf"><span>40 CFR 79.53 - Tier 2.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2013&page.go=Go">Code of Federal Regulations, 2013 CFR</a></p>
<p></p>
<p>2013-07-01</p>
<p>..., Salmonella typhimurium Reverse Mutation Assay). (b) Manufacturer determination. Manufacturers shall determine... Sister Chromatid Exchange Assay, and § 79.68 Salmonella typhimurium Reverse Mutation Assay. Teratogenic...</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2012-title40-vol17/pdf/CFR-2012-title40-vol17-sec79-53.pdf','CFR2012'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2012-title40-vol17/pdf/CFR-2012-title40-vol17-sec79-53.pdf"><span>40 CFR 79.53 - Tier 2.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2012&page.go=Go">Code of Federal Regulations, 2012 CFR</a></p>
<p></p>
<p>2012-07-01</p>
<p>..., Salmonella typhimurium Reverse Mutation Assay). (b) Manufacturer Determination. Manufacturers shall determine... Sister Chromatid Exchange Assay, and § 79.68 Salmonella typhimurium Reverse Mutation Assay. Teratogenic...</p>
</li>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2011-title40-vol16/pdf/CFR-2011-title40-vol16-sec79-53.pdf','CFR2011'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2011-title40-vol16/pdf/CFR-2011-title40-vol16-sec79-53.pdf"><span>40 CFR 79.53 - Tier 2.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2011&page.go=Go">Code of Federal Regulations, 2011 CFR</a></p>
<p></p>
<p>2011-07-01</p>
<p>..., Salmonella typhimurium Reverse Mutation Assay). (b) Manufacturer Determination. Manufacturers shall determine... Sister Chromatid Exchange Assay, and § 79.68 Salmonella typhimurium Reverse Mutation Assay. Teratogenic...</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2014-title40-vol17/pdf/CFR-2014-title40-vol17-sec79-53.pdf','CFR2014'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2014-title40-vol17/pdf/CFR-2014-title40-vol17-sec79-53.pdf"><span>40 CFR 79.53 - Tier 2.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2014&page.go=Go">Code of Federal Regulations, 2014 CFR</a></p>
<p></p>
<p>2014-07-01</p>
<p>..., Salmonella typhimurium Reverse Mutation Assay). (b) Manufacturer Determination. Manufacturers shall determine... Sister Chromatid Exchange Assay, and § 79.68 Salmonella typhimurium Reverse Mutation Assay. Teratogenic...</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol16/pdf/CFR-2010-title40-vol16-sec79-53.pdf','CFR'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol16/pdf/CFR-2010-title40-vol16-sec79-53.pdf"><span>40 CFR 79.53 - Tier 2.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2010&page.go=Go">Code of Federal Regulations, 2010 CFR</a></p>
<p></p>
<p>2010-07-01</p>
<p>..., Salmonella typhimurium Reverse Mutation Assay). (b) Manufacturer Determination. Manufacturers shall determine... Sister Chromatid Exchange Assay, and § 79.68 Salmonella typhimurium Reverse Mutation Assay. Teratogenic...</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/2009589','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/2009589"><span>Sister chromatid exchange in children of Seventh-Day Adventists and matched controls.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Hermansen, R; Waksvik, H; Fønnebø, V</p>
<p>1991-03-01</p>
<p>The low risk of cancer in Seventh-Day Adventists (SDAs) has been suggested to be due to genetic selection. To investigate this claim we examined the sister chromatid exchange (SCE) frequency in peripheral blood lymphocytes in 16 SDA children in Tromsø, all aged 0.5-8 years and 16 controls matched for sex and age. In 12 of 16 pairs, the SDA children had a lower SCE frequency than the controls. The mean difference was 4.06 (95% confidence interval -17.02-8.89, P = 0.51). There was no sex difference, and no correlation between age and SCE frequency. The genetic starting point with regard to SCE frequency seems to be the same for SDA children and controls.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4292170','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4292170"><span>DNA Strand Exchange and RecA Homologs in Meiosis</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Brown, M. Scott; Bishop, Douglas K.</p>
<p>2015-01-01</p>
<p>Homology search and DNA strand–exchange reactions are central to homologous recombination in meiosis. During meiosis, these processes are regulated such that the probability of choosing a homolog chromatid as recombination partner is enhanced relative to that of choosing a sister chromatid. This regulatory process occurs as homologous chromosomes pair in preparation for assembly of the synaptonemal complex. Two strand–exchange proteins, Rad51 and Dmc1, cooperate in regulated homology search and strand exchange in most organisms. Here, we summarize studies on the properties of these two proteins and their accessory factors. In addition, we review current models for the assembly of meiotic strand–exchange complexes and the possible mechanisms through which the interhomolog bias of recombination partner choice is achieved. PMID:25475089</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28947820','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28947820"><span>Mps1 kinase-dependent Sgo2 centromere localisation mediates cohesin protection in mouse oocyte meiosis I.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>El Yakoubi, Warif; Buffin, Eulalie; Cladière, Damien; Gryaznova, Yulia; Berenguer, Inés; Touati, Sandra A; Gómez, Rocío; Suja, José A; van Deursen, Jan M; Wassmann, Katja</p>
<p>2017-09-25</p>
<p>A key feature of meiosis is the step-wise removal of cohesin, the protein complex holding sister chromatids together, first from arms in meiosis I and then from the centromere region in meiosis II. Centromeric cohesin is protected by Sgo2 from Separase-mediated cleavage, in order to maintain sister chromatids together until their separation in meiosis II. Failures in step-wise cohesin removal result in aneuploid gametes, preventing the generation of healthy embryos. Here, we report that kinase activities of Bub1 and Mps1 are required for Sgo2 localisation to the centromere region. Mps1 inhibitor-treated oocytes are defective in centromeric cohesin protection, whereas oocytes devoid of Bub1 kinase activity, which cannot phosphorylate H2A at T121, are not perturbed in cohesin protection as long as Mps1 is functional. Mps1 and Bub1 kinase activities localise Sgo2 in meiosis I preferentially to the centromere and pericentromere respectively, indicating that Sgo2 at the centromere is required for protection.In meiosis I centromeric cohesin is protected by Sgo2 from Separase-mediated cleavage ensuring that sister chromatids are kept together until their separation in meiosis II. Here the authors demonstrate that Bub1 and Mps1 kinase activities are required for Sgo2 localisation to the centromere region.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20630917','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20630917"><span>Genotoxic assessment in peripheral blood lymphocytes of post-polio individuals using sister chromatid exchange analysis and micronucleus assay.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Bhattacharya, Saurabh Kumar; Saraswathy, Radha; Sivakumar, E</p>
<p>2011-07-01</p>
<p>Environmental pollution is a complex issue because of the diversity of anthropogenic agents, both chemical and physical, that have been detected and catalogued. The consequences to biota from exposure to genotoxic agents present an additional problem because of the potential for these agents to produce adverse change at the cellular and organism levels. Past studies in virus have focused on structural damage to the DNA of environmental species that may occur after exposure to genotoxic agents and the use of this information to document exposure and to monitor remediation. In an effort to predict effects at the population, community and ecosystem levels, in the present study, we attempt to characterize damage occurring through genotoxic agents like 5-bromo-2-deoxyuridine, BrdU, using sister chromatid exchange technique and the formation of micronuclei (MN) in the peripheral lymphocytes of the post-polio syndrome sequelae affected by poliovirus. Analysis of structural chromosomal aberrations (CAs) and involvement of the specific chromosome break were pursued in this study. They revealed a significantly higher incidence of CAs (chromatid and chromosome breaks) in patients compared with controls, where the specific chromosome break has emerged as specific. Also, the maximum numbers of breaks were found to be in chromosome 1 at the position 1p36.1. The results also suggest a correlation between CAs and content of MN.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/3365681','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/3365681"><span>Effect of betel chewing on the frequency of sister chromatid exchanges in pregnant women and women using oral contraceptives.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Ghosh, P K; Ghosh, R</p>
<p>1988-06-01</p>
<p>The incidence of sister chromatid exchange (SCE) was investigated in the lymphocyte chromosomes of betel chewing and non-chewing normal women, pregnant women, and women using oral contraceptives. The frequency of SCE was found to be 7.82 +/- 0.24 and 8.27 +/- 0.27 in non-chewing pregnant women and women using oral contraceptives respectively, which were significantly higher than the mean value of 5.21 +/- 0.18 observed in non-chewing normal women. Betel chewing induced higher SCE in pregnant women and women using oral contraceptives, the frequencies being 11.79 +/- 0.38 and 12.51 +/- 0.44, respectively, which were significantly higher than the SCE frequency of 6.28 +/- 0.21 found in normal betel chewing females.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/16131840','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/16131840"><span>Telomere sister chromatid exchange in telomerase deficient murine cells.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Wang, Yisong; Giannone, Richard J; Liu, Yie</p>
<p>2005-10-01</p>
<p>We have recently demonstrated that several types of genomic rearrangements (i.e., telomere sister chromatid exchange (T-SCE), genomic-SCE, or end-to-end fusions) were more often detected in long-term cultured murine telomerase deficient embryonic stem (ES) cells than in freshly prepared murine splenocytes, even through they possessed similar frequencies of critically short telomeres. The high rate of genomic rearrangements in telomerase deficient ES cells, when compared to murine splenocytes, may reflect the cultured cells' gained ability to protect chromosome ends with eroded telomeres allowing them to escape "end crisis". However, the possibility that ES cells were more permissive to genomic rearrangements than other cell types or that differences in the microenvironment or genetic background of the animals might consequentially determine the rate of T-SCEs or other genomic rearrangements at critically short telomeres could not be ruled out.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=20040088723&hterms=incubation&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D60%26Ntt%3Dincubation','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=20040088723&hterms=incubation&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D60%26Ntt%3Dincubation"><span>Rejoining of isochromatid breaks induced by heavy ions in G2-phase normal human fibroblasts</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p>
<p>Kawata, T.; Durante, M.; Furusawa, Y.; George, K.; Ito, H.; Wu, H.; Cucinotta, F. A.</p>
<p>2001-01-01</p>
<p>We reported previously that exposure of normal human fibroblasts in G2 phase of the cell cycle to high-LET radiation produces a much higher frequency of isochromatid breaks than exposure to gamma rays. We concluded that an increase in the production of isochromatid breaks is a signature of initial high-LET radiation-induced G2-phase damage. In this paper, we report the repair kinetics of isochromatid breaks induced by high-LET radiation in normal G2-phase human fibroblasts. Exponentially growing human fibroblasts (AG1522) were irradiated with gamma rays or energetic carbon (290 MeV/nucleon), silicon (490 MeV/nucleon), or iron (200 MeV/nucleon) ions. Prematurely condensed chromosomes were induced by calyculin A after different postirradiation incubation times ranging from 0 to 600 min. Chromosomes were stained with Giemsa, and aberrations were scored in cells at G2 phase. G2-phase fragments, the result of the induction of isochromatid breaks, decreased quickly with incubation time. The curve for the kinetics of the rejoining of chromatid-type breaks showed a slight upward curvature with time after exposure to 440 keV/microm iron particles, probably due to isochromatid-isochromatid break rejoining. The formation of chromatid exchanges after exposure to high-LET radiation therefore appears to be underestimated, because isochromatid-isochromatid exchanges cannot be detected. Increased induction of isochromatid breaks and rejoining of isochromatid breaks affect the overall kinetics of chromatid-type break rejoining after exposure to high-LET radiation.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4199692','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4199692"><span>Regulation of Centromere Localization of the Drosophila Shugoshin MEI-S332 and Sister-Chromatid Cohesion in Meiosis</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Nogueira, Cristina; Kashevsky, Helena; Pinto, Belinda; Clarke, Astrid; Orr-Weaver, Terry L.</p>
<p>2014-01-01</p>
<p>The Shugoshin (Sgo) protein family helps to ensure proper chromosome segregation by protecting cohesion at the centromere by preventing cleavage of the cohesin complex. Some Sgo proteins also influence other aspects of kinetochore-microtubule attachments. Although many Sgo members require Aurora B kinase to localize to the centromere, factors controlling delocalization are poorly understood and diverse. Moreover, it is not clear how Sgo function is inactivated and whether this is distinct from delocalization. We investigated these questions in Drosophila melanogaster, an organism with superb chromosome cytology to monitor Sgo localization and quantitative assays to test its function in sister-chromatid segregation in meiosis. Previous research showed that in mitosis in cell culture, phosphorylation of the Drosophila Sgo, MEI-S332, by Aurora B promotes centromere localization, whereas Polo phosphorylation promotes delocalization. These studies also suggested that MEI-S332 can be inactivated independently of delocalization, a conclusion supported here by localization and function studies in meiosis. Phosphoresistant and phosphomimetic mutants for the Aurora B and Polo phosphorylation sites were examined for effects on MEI-S332 localization and chromosome segregation in meiosis. Strikingly, MEI-S332 with a phosphomimetic mutation in the Aurora B phosphorylation site prematurely dissociates from the centromeres in meiosis I. Despite the absence of MEI-S332 on meiosis II centromeres in male meiosis, sister chromatids segregate normally, demonstrating that detectable levels of this Sgo are not essential for chromosome congression, kinetochore biorientation, or spindle assembly. PMID:25081981</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/6865499','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/6865499"><span>Cyclophosphamide-induced in vivo sister chromatid exchange in Mus Musculus. II: Effect of age and genotype on sister chromatid exchange, micronuclei and metaphase index.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Reimer, D L; Singh, S M</p>
<p>1983-01-01</p>
<p>In vivo cyclophosphamide-induced sister chromatid exchanges (SCEs) micronuclei, and metaphase indices were assessed in two age groups (10.8 +/- 0.9 weeks' an 33.1 +/- 1.3 weeks' old) of female mice from three genetic strains (C3H/S, C57BL/6J, and Balb/c). In general, older animals showed diminished SCE induction over their younger counterparts. The relative difference between individuals of the two ages is strain-dependent. Unlike C57BL/6J and Balb/c, strain C3H/S showed significantly lower SCE values in the older animals at every cyclophosphamide treatment. It may reflect on the possible involvement of genetic determinant(s) for the component(s) of SCE formation during aging. Frequencies of micronuclei, however, were consistently higher in older animals than in their younger counterparts. Furthermore, cytotoxicity of cyclophosphamide, as reflected in metaphase indices, was also higher in older animals. Lower metaphase indices associated with higher micronuclei levels in older individuals may suggest a decline in the rate of cellular replication in these animals. Furthermore, the lower metaphase indices associated with lower SCE values, and increasing micronuclei levels accompanied by decreasing SCE frequencies in older animals, may reflect reduced DNA repair ability during aging. These results support the hypothesis of genotype-dependent decline in the rate of DNA repair and replication during aging, particularly under stressed conditions.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2016APS..MARA41004R','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2016APS..MARA41004R"><span>On the robustness of SAC silencing in closed mitosis</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p>
<p>Ruth, Donovan; Liu, Jian</p>
<p></p>
<p>Mitosis equally partitions sister chromatids to two daughter cells. This is achieved by properly attaching these chromatids via their kinetochores to microtubules that emanate from the spindle poles. Once the last kinetochore is properly attached, the spindle microtubules pull the sister chromatids apart. Due to the dynamic nature of microtubules, however, kinetochore-microtubule attachment often goes wrong. When this erroneous attachment occurs, it locally activates an ensemble of proteins, called the spindle assembly checkpoint proteins (SAC), which halts the mitotic progression until all the kinetochores are properly attached by spindle microtubules. The timing of SAC silencing thus determines the fidelity of chromosome segregation. We previously established a spatiotemporal model that addresses the robustness of SAC silencing in open mitosis for the first time. Here, we focus on closed mitosis by examining yeast mitosis as a model system. Though much experimental work has been done to study the SAC in cells undergoing closed mitosis, the processes responsible are not well understood. We leverage and extend our previous model to study SAC silencing mechanism in closed mitosis. We show that a robust signal of the SAC protein accumulation at the spindle pole body can be achieved. This signal is a nonlinear increasing function of number of kinetochore-microtubule attachments, and can thus serve as a robust trigger to time the SAC silencing. Together, our mechanism provides a unified framework across species that ensures robust SAC silencing and fidelity of chromosome segregation in mitosis. Intramural research program in NHLBI at NIH.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=35277','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=35277"><span>The C-terminal domain of the Bloom syndrome DNA helicase is essential for genomic stability</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Yankiwski, Victor; Noonan, James P; Neff, Norma F</p>
<p>2001-01-01</p>
<p>Background Bloom syndrome is a rare cancer-prone disorder in which the cells of affected persons have a high frequency of somatic mutation and genomic instability. Bloom syndrome cells have a distinctive high frequency of sister chromatid exchange and quadriradial formation. BLM, the protein altered in BS, is a member of the RecQ DNA helicase family, whose members share an average of 40% identity in the helicase domain and have divergent N-terminal and C-terminal flanking regions of variable lengths. The BLM DNA helicase has been shown to localize to the ND10 (nuclear domain 10) or PML (promyelocytic leukemia) nuclear bodies, where it associates with TOPIIIα, and to the nucleolus. Results This report demonstrates that the N-terminal domain of BLM is responsible for localization of the protein to the nuclear bodies, while the C-terminal domain directs the protein to the nucleolus. Deletions of the N-terminal domain of BLM have little effect on sister chromatid exchange frequency and chromosome stability as compared to helicase and C-terminal mutations which can increase SCE frequency and chromosome abnormalities. Conclusion The helicase activity and the C-terminal domain of BLM are critical for maintaining genomic stability as measured by the sister chromatid exchange assay. The localization of BLM into the nucleolus by the C-terminal domain appears to be more important to genomic stability than localization in the nuclear bodies. PMID:11472631</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/7688857','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/7688857"><span>Sister-chromatid exchanges and cell-cycle kinetics in the lymphocytes of workers occupationally exposed to a chemical mixture in the tyre industry.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Sasiadek, M</p>
<p>1993-08-01</p>
<p>Cytogenetic studies of clinically healthy workers employed in the rubber industry showed an increase in chromosome aberrations (CAs), sister-chromatid exchanges (SCEs) and a decrease in proliferation indices (PIs). The aim of the present study was to establish, using the SCE and PI tests, genotoxic effects of hazardous chemicals in the rubber industry. An increase in mean SCEs in the lymphocytes of vulcanizers as compared to controls was observed. Since the PI in the exposed group was insignificantly decreased as compared to the controls, it could be concluded that the SCE test is the most sensitive cytogenetic test for the detection of a genotoxic effect of chemicals in the rubber industry. There was no evidence in the present study that the genotoxic effect of chemicals in the rubber industry was enhanced by cigarette smoking.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/1427859-structural-evidence-scc4-dependent-localization-cohesin-loading','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/1427859-structural-evidence-scc4-dependent-localization-cohesin-loading"><span></span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Hinshaw, Stephen M.; Makrantoni, Vasso; Kerr, Alastair</p>
<p></p>
<p>The cohesin ring holds newly replicated sister chromatids together until their separation at anaphase. Initiation of sister chromatid cohesion depends on a separate complex, Scc2NIPBL/Scc4Mau2 (Scc2/4), which loads cohesin onto DNA and determines its localization across the genome. Proper cohesin loading is essential for cell division, and partial defects cause chromosome missegregation and aberrant transcriptional regulation, leading to severe developmental defects in multicellular organisms. We present here a crystal structure showing the interaction between Scc2 and Scc4. Scc4 is a TPR array that envelops an extended Scc2 peptide. Using budding yeast, we demonstrate that a conserved patch on the surfacemore » of Scc4 is required to recruit Scc2/4 to centromeres and to build pericentromeric cohesion. These findings reveal the role of Scc4 in determining the localization of cohesin loading and establish a molecular basis for Scc2/4 recruitment to centromeres.« less</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/978252-telomere-sister-chromatid-exchange-telomerase-deficient-murine-cells','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/978252-telomere-sister-chromatid-exchange-telomerase-deficient-murine-cells"><span>Telomere sister chromatid exchange in telomerase deficient murine cells</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Wang, Yisong; Giannone, Richard J; Liu, Yie</p>
<p>2005-01-01</p>
<p>We have recently demonstrated that several types of genomic rearrangements (i.e., telomere sister chromatid exchange (T-SCE), genomic-SCE, or end-to-end fusions) were more often detected in long-term cultured murine telomerase deficient embryonic stem (ES) cells than in freshly prepared murine splenocytes, even through they possessed similar frequencies of critically short telomeres. The high rate of genomic rearrangements in telomerase deficient ES cells, when compared to murine splenocytes, may reflect the cultured cells' gained ability to protect chromosome ends with eroded telomeres allowing them to escape 'end crisis'. However, the possibility that ES cells were more permissive to genomic rearrangements than othermore » cell types or that differences in the microenvironment or genetic background of the animals might consequentially determine the rate of T-SCEs or other genomic rearrangements at critically short telomeres could not be ruled out.« less</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19345191','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19345191"><span>Separase is recruited to mitotic chromosomes to dissolve sister chromatid cohesion in a DNA-dependent manner.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Sun, Yuxiao; Kucej, Martin; Fan, Heng-Yu; Yu, Hong; Sun, Qing-Yuan; Zou, Hui</p>
<p>2009-04-03</p>
<p>Sister chromatid separation is triggered by the separase-catalyzed cleavage of cohesin. This process is temporally controlled by cell-cycle-dependent factors, but its biochemical mechanism and spatial regulation remain poorly understood. We report that cohesin cleavage by human separase requires DNA in a sequence-nonspecific manner. Separase binds to DNA in vitro, but its proteolytic activity, measured by its autocleavage, is not stimulated by DNA. Instead, biochemical characterizations suggest that DNA mediates cohesin cleavage by bridging the interaction between separase and cohesin. In human cells, a fraction of separase localizes to the mitotic chromosome. The importance of the chromosomal DNA in cohesin cleavage is further demonstrated by the observation that the cleavage of the chromosome-associated cohesins is sensitive to nuclease treatment. Our observations explain why chromosome-associated cohesins are specifically cleaved by separase and the soluble cohesins are left intact in anaphase.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/6872102','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/6872102"><span>Alkaline DNA fragmentation, DNA disentanglement evaluated viscosimetrically and sister chromatid exchanges, after treatment in vivo with nitrofurantoin.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Parodi, S; Pala, M; Russo, P; Balbi, C; Abelmoschi, M L; Taningher, M; Zunino, A; Ottaggio, L; de Ferrari, M; Carbone, A; Santi, L</p>
<p>1983-07-01</p>
<p>Nitrofurantoin was not positive as a carcinogen in long term assays. In vitro it was positive in some short term tests and negative in others. We have examined Nitrofurantoin for its capability of inducing DNA damage in vivo. With the alkaline elution technique, Nitrofurantoin appeared clearly positive in all the tissues examined (liver, kidney, lung, spleen and bone marrow). In the liver we also observed some cross-linking effect. In bone marrow cells Nitrofurantoin was also clearly positive in terms of sister chromatid exchanges (SCEs) induction. DNA damage in vivo was also examined with a viscosimetric method, more sensitive than alkaline elution. With this method the results were essentially negative, suggesting that the two methods detect different types of damage. In view of its positivity in many organs and in two short term tests in vivo, the carcinogenic potential of Nitrofurantoin should be reconsidered.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5088565','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5088565"><span>Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Martin, Carol-Anne; Murray, Jennie E.; Carroll, Paula; Leitch, Andrea; Mackenzie, Karen J.; Halachev, Mihail; Fetit, Ahmed E.; Keith, Charlotte; Bicknell, Louise S.; Fluteau, Adeline; Gautier, Philippe; Hall, Emma A.; Joss, Shelagh; Soares, Gabriela; Silva, João; Bober, Michael B.; Duker, Angela; Wise, Carol A.; Quigley, Alan J.; Phadke, Shubha R.; Wood, Andrew J.; Vagnarelli, Paola; Jackson, Andrew P.</p>
<p>2016-01-01</p>
<p>Compaction of chromosomes is essential for accurate segregation of the genome during mitosis. In vertebrates, two condensin complexes ensure timely chromosome condensation, sister chromatid disentanglement, and maintenance of mitotic chromosome structure. Here, we report that biallelic mutations in NCAPD2, NCAPH, or NCAPD3, encoding subunits of these complexes, cause microcephaly. In addition, hypomorphic Ncaph2 mice have significantly reduced brain size, with frequent anaphase chromatin bridge formation observed in apical neural progenitors during neurogenesis. Such DNA bridges also arise in condensin-deficient patient cells, where they are the consequence of failed sister chromatid disentanglement during chromosome compaction. This results in chromosome segregation errors, leading to micronucleus formation and increased aneuploidy in daughter cells. These findings establish “condensinopathies” as microcephalic disorders, with decatenation failure as an additional disease mechanism for microcephaly, implicating mitotic chromosome condensation as a key process ensuring mammalian cerebral cortex size. PMID:27737959</p>
</li>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26923589','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26923589"><span>Structure of the Pds5-Scc1 Complex and Implications for Cohesin Function.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Muir, Kyle W; Kschonsak, Marc; Li, Yan; Metz, Jutta; Haering, Christian H; Panne, Daniel</p>
<p>2016-03-08</p>
<p>Sister chromatid cohesion is a fundamental prerequisite to faithful genome segregation. Cohesion is precisely regulated by accessory factors that modulate the stability with which the cohesin complex embraces chromosomes. One of these factors, Pds5, engages cohesin through Scc1 and is both a facilitator of cohesion, and, conversely also mediates the release of cohesin from chromatin. We present here the crystal structure of a complex between budding yeast Pds5 and Scc1, thus elucidating the molecular basis of Pds5 function. Pds5 forms an elongated HEAT repeat that binds to Scc1 via a conserved surface patch. We demonstrate that the integrity of the Pds5-Scc1 interface is indispensable for the recruitment of Pds5 to cohesin, and that its abrogation results in loss of sister chromatid cohesion and cell viability. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5068846','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5068846"><span>Restructuring of Holocentric Centromeres During Meiosis in the Plant Rhynchospora pubera</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Marques, André; Schubert, Veit; Houben, Andreas; Pedrosa-Harand, Andrea</p>
<p>2016-01-01</p>
<p>Centromeres are responsible for the correct segregation of chromosomes during mitosis and meiosis. Holocentric chromosomes, characterized by multiple centromere units along each chromatid, have particular adaptations to ensure regular disjunction during meiosis. Here we show by detecting CENH3, CENP-C, tubulin, and centromeric repeats that holocentromeres may be organized differently in mitosis and meiosis of Rhynchospora pubera. Contrasting to the mitotic linear holocentromere organization, meiotic centromeres show several clusters of centromere units (cluster-holocentromeres) during meiosis I. They accumulate along the poleward surface of bivalents where spindle fibers perpendicularly attach. During meiosis II, the cluster-holocentromeres are mostly present in the midregion of each chromatid. A linear holocentromere organization is restored after meiosis during pollen mitosis. Thus, a not yet described case of a cluster-holocentromere organization, showing a clear centromere restructuration between mitosis and meiosis, was identified in a holocentric organism. PMID:27489000</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27489000','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27489000"><span>Restructuring of Holocentric Centromeres During Meiosis in the Plant Rhynchospora pubera.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Marques, André; Schubert, Veit; Houben, Andreas; Pedrosa-Harand, Andrea</p>
<p>2016-10-01</p>
<p>Centromeres are responsible for the correct segregation of chromosomes during mitosis and meiosis. Holocentric chromosomes, characterized by multiple centromere units along each chromatid, have particular adaptations to ensure regular disjunction during meiosis. Here we show by detecting CENH3, CENP-C, tubulin, and centromeric repeats that holocentromeres may be organized differently in mitosis and meiosis of Rhynchospora pubera Contrasting to the mitotic linear holocentromere organization, meiotic centromeres show several clusters of centromere units (cluster-holocentromeres) during meiosis I. They accumulate along the poleward surface of bivalents where spindle fibers perpendicularly attach. During meiosis II, the cluster-holocentromeres are mostly present in the midregion of each chromatid. A linear holocentromere organization is restored after meiosis during pollen mitosis. Thus, a not yet described case of a cluster-holocentromere organization, showing a clear centromere restructuration between mitosis and meiosis, was identified in a holocentric organism. Copyright © 2016 by the Genetics Society of America.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=25194','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=25194"><span>The DNA Helicase Activity of BLM Is Necessary for the Correction of the Genomic Instability of Bloom Syndrome Cells</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Neff, Norma F.; Ellis, Nathan A.; Ye, Tian Zhang; Noonan, James; Huang, Kelly; Sanz, Maureen; Proytcheva, Maria</p>
<p>1999-01-01</p>
<p>Bloom syndrome (BS) is a rare autosomal recessive disorder characterized by growth deficiency, immunodeficiency, genomic instability, and the early development of cancers of many types. BLM, the protein encoded by BLM, the gene mutated in BS, is localized in nuclear foci and absent from BS cells. BLM encodes a DNA helicase, and proteins from three missense alleles lack displacement activity. BLM transfected into BS cells reduces the frequency of sister chromatid exchanges and restores BLM in the nucleus. Missense alleles fail to reduce the sister chromatid exchanges in transfected BS cells or restore the normal nuclear pattern. BLM complements a phenotype of a Saccharomyces cerevisiae sgs1 top3 strain, and the missense alleles do not. This work demonstrates the importance of the enzymatic activity of BLM for its function and nuclear localization pattern. PMID:10069810</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2139799','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2139799"><span>Thrombopoietin-induced Polyploidization of Bone Marrow Megakaryocytes Is Due to a Unique Regulatory Mechanism in Late Mitosis</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Nagata, Yuka; Muro, Yoshinao; Todokoro, Kazuo</p>
<p>1997-01-01</p>
<p>Megakaryocytes undergo a unique differentiation program, becoming polyploid through repeated cycles of DNA synthesis without concomitant cell division. However, the mechanism underlying this polyploidization remains totally unknown. It has been postulated that polyploidization is due to a skipping of mitosis after each round of DNA replication. We carried out immunohistochemical studies on mouse bone marrow megakaryocytes during thrombopoietin- induced polyploidization and found that during this process megakaryocytes indeed enter mitosis and progress through normal prophase, prometaphase, metaphase, and up to anaphase A, but not to anaphase B, telophase, or cytokinesis. It was clearly observed that multiple spindle poles were formed as the polyploid megakaryocytes entered mitosis; the nuclear membrane broke down during prophase; the sister chromatids were aligned on a multifaced plate, and the centrosomes were symmetrically located on either side of each face of the plate at metaphase; and a set of sister chromatids moved into the multiple centrosomes during anaphase A. We further noted that the pair of spindle poles in anaphase were located in close proximity to each other, probably because of the lack of outward movement of spindle poles during anaphase B. Thus, the reassembling nuclear envelope may enclose all the sister chromatids in a single nucleus at anaphase and then skip telophase and cytokinesis. These observations clearly indicate that polyploidization of megakaryocytes is not simply due to a skipping of mitosis, and that the megakaryocytes must have a unique regulatory mechanism in anaphase, e.g., factors regulating anaphase such as microtubule motor proteins might be involved in this polyploidization process. PMID:9334347</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22735043','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22735043"><span>CDC-48/p97 is required for proper meiotic chromosome segregation via controlling AIR-2/Aurora B kinase localization in Caenorhabditis elegans.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Sasagawa, Yohei; Higashitani, Atsushi; Urano, Takeshi; Ogura, Teru; Yamanaka, Kunitoshi</p>
<p>2012-08-01</p>
<p>CDC-48/p97 is a AAA (ATPases associated with diverse cellular activities) chaperone involved in protein conformational changes such as the disassembly of protein complexes. We previously reported that Caenorhabditis elegans CDC-48.1 and CDC-48.2 (CDC-48s) are essential for the progression of meiosis I metaphase. Here, we report that CDC-48s are required for proper chromosome segregation during meiosis in C. elegans. In wild-type worms, at the diakinesis phase, phosphorylation of histone H3, one of the known substrates of aurora B kinase (AIR-2), on meiosis I chromatids correlated with AIR-2 localization at the cohesion sites of homologous chromatids. Conversely, depletion of CDC-48s resulted in a significant expansion of signals for AIR-2 and phosphorylated histone H3 over the entire length of meiotic chromosomes, leading to defective chromosome segregation, while the total amount of AIR-2 in lysates was not changed by the depletion of CDC-48s. The defective segregation of meiotic chromosomes caused by the depletion of CDC-48s was suppressed by the simultaneous depletion of AIR-2 and is similar to that observed following the depletion of protein phosphatase 1 (PP1) phosphatases. However, the amount and localization of PP1 were not changed by the depletion of CDC-48s. These results suggest that CDC-48s control the restricted localization of AIR-2 to the cohesion sites of homologous chromatids in meiosis I. Copyright © 2012 Elsevier Inc. All rights reserved.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/22210259-sumo-protease-senp1-required-cohesion-maintenance-mitotic-arrest-following-spindle-poison-treatment','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22210259-sumo-protease-senp1-required-cohesion-maintenance-mitotic-arrest-following-spindle-poison-treatment"><span></span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Era, Saho; Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501; Abe, Takuya</p>
<p></p>
<p>Highlights: Black-Right-Pointing-Pointer SENP1 knockout chicken DT40 cells are hypersensitive to spindle poisons. Black-Right-Pointing-Pointer Spindle poison treatment of SENP1{sup -/-} cells leads to increased mitotic slippage. Black-Right-Pointing-Pointer Mitotic slippage in SENP1{sup -/-} cells associates with apoptosis and endoreplication. Black-Right-Pointing-Pointer SENP1 counteracts sister chromatid separation during mitotic arrest. Black-Right-Pointing-Pointer Plk1-mediated cohesion down-regulation is involved in colcemid cytotoxicity. -- Abstract: SUMO conjugation is a reversible posttranslational modification that regulates protein function. SENP1 is one of the six SUMO-specific proteases present in vertebrate cells and its altered expression is observed in several carcinomas. To characterize SENP1 role in genome integrity, we generated Senp1 knockoutmore » chicken DT40 cells. SENP1{sup -/-} cells show normal proliferation, but are sensitive to spindle poisons. This hypersensitivity correlates with increased sister chromatid separation, mitotic slippage, and apoptosis. To test whether the cohesion defect had a causal relationship with the observed mitotic events, we restored the cohesive status of sister chromatids by introducing the TOP2{alpha}{sup +/-} mutation, which leads to increased catenation, or by inhibiting Plk1 and Aurora B kinases that promote cohesin release from chromosomes during prolonged mitotic arrest. Although TOP2{alpha} is SUMOylated during mitosis, the TOP2{alpha}{sup +/-} mutation had no obvious effect. By contrast, inhibition of Plk1 or Aurora B rescued the hypersensitivity of SENP1{sup -/-} cells to colcemid. In conclusion, we identify SENP1 as a novel factor required for mitotic arrest and cohesion maintenance during prolonged mitotic arrest induced by spindle poisons.« less</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/978251-increase-telomere-sister-chromatid-exchange-murine-embryonic-stem-cells-possessing-critically-shortened-telomeres','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/978251-increase-telomere-sister-chromatid-exchange-murine-embryonic-stem-cells-possessing-critically-shortened-telomeres"><span>An increase in telomere sister chromatid exchange in murine embryonic stem cells possessing critically shortened telomeres</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Wang, Yisong; Giannone, Richard J; Wu, Jun</p>
<p></p>
<p>Telomerase deficiency leads to a progressive loss of telomeric DNA that eventually triggers cell apoptosis in human primary cells during prolonged growth in culture. Rare survivors can maintain telomere length through either activation of telomerase or recombination-based telomere lengthening, and thus proliferate indefinitely. We have explored the possibility that telomeres may be maintained through telomere sister chromatid exchange (T-SCE) in murine telomere reverse transcriptase-deficient (mTert -/-) splenocytes and ES cells. Because telomerase deficiency leads to gradual loss of telomeric DNA in mTert -/- splenocytes and ES cells and eventually to chromosomes with telomere signal-free ends (SFEs), we examined these cellmore » types for evidence of sister chromatid exchange at telomeres, and observed an increase in T-SCEs only in a subset of mTert -/- splenocytes or ES cells that possessed multiple SFEs. Furthermore, T-SCEs were more often detected in ES cells than in splenocytes that harbored a similar frequency of SFEs. In mTert heterozygous (mTert +/-) ES cells or splenocytes, which are known to exhibit a decrease in average telomere length but no SFEs, no increase in T-SCE was observed. In addition to T-SCE, other genomic rearrangements (i.e., SCE) were also significantly increased in mTert -/- ES cells possessing critically short telomeres, but not in splenocytes. Our results suggest that animals and cell culture differ in their ability to carry out genomic rearrangements as a means of maintaining telomere integrity when telomeres become critically shortened.« less</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/661839','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/661839"><span>Chromosome-damaging effect of betel leaf.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Sadasivan, G; Rani, G; Kumari, C K</p>
<p>1978-05-01</p>
<p>The chewing of betel leaf with other ingredients is a widespread addiction in India. The chromosome damaging effect was studied in human leukocyte cultures. There was an increase in the frequency of chromatid aberrations when the leaf extract was added to cultures.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1216365','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1216365"><span>Lack of Spontaneous Sister Chromatid Exchanges in Somatic Cells of DROSOPHILA MELANOGASTER</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Gatti, M.; Santini, G.; Pimpinelli, S.; Olivieri, G.</p>
<p>1979-01-01</p>
<p>Neural ganglia of wild type third-instar larvae of Drosophila melanogaster were incubated for 13 hours at various concentrations of BUdR (1, 3, 9, 27 µg/ml). Metaphases were collected with colchicine, stained with Hoechst 33258, and scored under a fluorescence microscope. Metaphases in which the sister chromatids were clearly differentiated were scored for the presence of sister-chromatid exchanges (SCEs). At the lowest concentration of BUdR (1 µg/ml), no SCEs were observed in either male or female neuroblasts. The SCEs were found at the higher concentrations of BUdR (3, 9 and 27 µg/ml) and with a greater frequency in females than in males. Therefore SCEs are not a spontaneous phenomenon in D. melanogaster, but are induced by BUdR incorporated in the DNA. A striking nonrandomness was found in the distribution of SCEs along the chromosomes. More than a third of the SCEs were clustered in the junctions between euchromatin and heterochromatin. The remaining SCEs were preferentially localized within the heterochromatic regions of the X chromosome and the autosomes and primarily on the entirely heterochromatic Y chromosome.—In order to find an alternative way of measuring the frequency of SCEs in Drosophila neuroblasts, the occurrence of double dicentric rings was studied in two stocks carrying monocentric ring-X chromosomes. One ring chromosome, C(1)TR 94–2, shows a rate of dicentric ring formation corresponding to the frequency of SCEs observed in the BUdR-labelled rod chromosomes. The other ring studied, R(1)2, exhibits a frequency of SCEs higher than that observed with both C(1)TR 94–2 and rod chromosomes. PMID:109350</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/3731084','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/3731084"><span>Abnormally banded chromosomal regions in doxorubicin-resistant B16-BL6 murine melanoma cells.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Slovak, M L; Hoeltge, G A; Ganapathi, R</p>
<p>1986-08-01</p>
<p>B16-BL6 murine melanoma cells were selected for cytogenetic evaluation during the stepwise development of increasing resistance in vitro to the antitumor antibiotic, doxorubicin (DOX). Karyotypic studies demonstrated extensive heteroploidy with both numerical and structural abnormalities which were not present in the parental DOX-sensitive B16-BL6 cells. Trypsin-Giemsa banding revealed the presence of several marker chromosomes containing abnormally banding regions (ABRs) in the 44-fold B16-BL6 DOX-resistant subline. These ABRs appeared to be more homogeneously staining at the higher DOX concentrations. Length measurements (ABR index) in seven banded metaphases indicated a direct correlation with increasing DOX concentration. When the DOX-resistant cells were grown in drug-free medium for 1 yr, the drug-resistant phenotype gradually declined in parallel with the level of resistance and the ABR index. DOX-induced cytogenetic damage examined by sister chromatid exchange methodology in parental B16-BL6 cells indicated a linear sister chromatid exchange:DOX dose-response relationship. However, after continuous treatment of parental B16-BL6 cells with DOX (0.01 microgram/ml) for 30 days, sister chromatid exchange scores were found to return to base-line values. The B16-BL6 resistant cells demonstrated a cross-resistant phenotype with N-trifluoroacetyladriamycin-14-valerate, actinomycin D, and the Vinca alkaloids but not with 1-beta-D-arabinofuranosylcytosine. The results suggest that ABR-containing chromosomes in DOX-resistant sublines may represent cytogenetic alterations of specific amplified genes involved in the expression of DOX resistance. Further studies are required to identify and define the possible gene products and to correlate their relationship to the cytotoxic action of doxorubicin.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/7508088','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/7508088"><span>Chromosome damage in lymphocytes of stainless steel welders related to past and current exposure to manual metal arc welding fumes.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Jelmert, O; Hansteen, I L; Langård, S</p>
<p>1994-02-01</p>
<p>Cytogenetic damage was studied in lymphocytes from 42 welders using the manual metal arc (MMA) method on stainless steel (SS). A detailed characterization of previous exposure by job interviews, and for current exposure with personal air sampling and biological monitoring of chromium (Cr) and nickel (Ni) in blood and urine, was done for 32 of these welders. A subgroup of 20 welders was studied before and after 1-4 months of MMA/SS welding. A matched reference group I, and a larger reference group II were established for comparison. A significant increase in chromatid breaks (1.4 vs. 0.9 and 0.8 for group I and II) and for cells with aberrations (2.2 vs. 1.6 in group II) was found in the welders. An even larger difference was found when comparing non-smoking welders with their non-smoking referents. No synergistic effect between smoking and MMA/SS welding fumes was observed for any type of aberrations. Current welding fume exposure during the week before sampling was not associated with increases in any type of cytogenetic damage. The results indicated that the increase in chromatid breaks was associated with cumulated welding fume exposure for more than a year, and with not using respirators. Exposure to MMA/SS welding fumes for up to 4 months gave a slight, but significant increase in chromatid breaks when using the welders as their own referents. However, when using matched referents in the study after exposure, no difference was found between these welders and their matched referents. No differences between the groups were observed in the DNA synthesis and repair-inhibited cultures or for SCE.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2734174','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2734174"><span>The Cellular Phenotype of Roberts Syndrome Fibroblasts as Revealed by Ectopic Expression of ESCO2</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>van der Lelij, Petra; van Gosliga, Djoke; Oostra, Anneke B.; Steltenpool, Jûrgen; de Groot, Jan; Scheper, Rik J.; Wolthuis, Rob M.; Waisfisz, Quinten; Darroudi, Firouz; Joenje, Hans; de Winter, Johan P.</p>
<p>2009-01-01</p>
<p>Cohesion between sister chromatids is essential for faithful chromosome segregation. In budding yeast, the acetyltransferase Eco1/Ctf7 establishes cohesion during DNA replication in S phase and in response to DNA double strand breaks in G2/M phase. In humans two Eco1 orthologs exist: ESCO1 and ESCO2. Both proteins are required for proper sister chromatid cohesion, but their exact function is unclear at present. Since ESCO2 has been identified as the gene defective in the rare autosomal recessive cohesinopathy Roberts syndrome (RBS), cells from RBS patients can be used to elucidate the role of ESCO2. We investigated for the first time RBS cells in comparison to isogenic controls that stably express V5- or GFP-tagged ESCO2. We show that the sister chromatid cohesion defect in the transfected cell lines is rescued and suggest that ESCO2 is regulated by proteasomal degradation in a cell cycle-dependent manner. In comparison to the corrected cells RBS cells were hypersensitive to the DNA-damaging agents mitomycin C, camptothecin and etoposide, while no particular sensitivity to UV, ionizing radiation, hydroxyurea or aphidicolin was found. The cohesion defect of RBS cells and their hypersensitivity to DNA-damaging agents were not corrected by a patient-derived ESCO2 acetyltransferase mutant (W539G), indicating that the acetyltransferase activity of ESCO2 is essential for its function. In contrast to a previous study on cells from patients with Cornelia de Lange syndrome, another cohesinopathy, RBS cells failed to exhibit excessive chromosome aberrations after irradiation in G2 phase of the cell cycle. Our results point at an S phase-specific role for ESCO2 in the maintenance of genome stability. PMID:19738907</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20730658','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20730658"><span>Increased frequency of sister chromatid exchanges and decrease in cell viability and proliferation kinetics in human peripheral blood lymphocytes after in vitro exposure to whole bee venom.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Gajski, Goran; Garaj-Vrhovac, Vera</p>
<p>2010-10-01</p>
<p>The present study was aimed to investigate the impact of bee venom on frequency of sister chromatid exchanges (SCE) and viability in human peripheral blood lymphocytes in vitro. In addition, the proportion of lymphocytes that undergo one, two or three cell divisions as well as proliferative rate index (PRI) have been determined. Aqueous solution of whole bee venom was added to whole blood samples in concentrations ranging from 0.1 microg/mL to 20 microg/mL in different lengths of time. Results showed that whole bee venom inhibited cell viability, resulting in a 22.86 +/- 1.14% and 51.21 +/- 0.58% reduction of viable cells at 1 hour and 6 hours, respectively. The mean SCE per cell in all the exposed samples was significantly higher than in the corresponding controls. In addition, the percentage of high frequency cells (HFC) for each sample was estimated using the pooled distribution of all SCE measurements. This parameter was also significantly higher compared to the control. Inhibition of proliferation was statistically significant for both exposure times and concentrations and was time and dose dependent. These data indicate that whole bee venom inhibited cell proliferation, resulting in a 36.87 +/- 5.89% and 38.43 +/- 1.96% reduction of proliferation at 1 hour and 6 hours, respectively. In conclusion, this report demonstrated that whole bee venom is capable of inducing DNA alterations by virtue of increasing sister chromatid exchanges in addition to the cell viability decrease and inhibition of proliferation kinetics in human peripheral blood lymphocytes in vitro.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=65716&keyword=donor+AND+blood&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50','EPA-EIMS'); return false;" href="https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=65716&keyword=donor+AND+blood&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50"><span>INDUCTION OF DNA STRAND BREAKS BY TRIHALOMETHANES IN PRIMARY HUMAN LUNG EPITHELIAL CELLS</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://oaspub.epa.gov/eims/query.page">EPA Science Inventory</a></p>
<p></p>
<p></p>
<p><br>Abstract<br><br> Trihalomethanes (TEMs) are disinfection by-products and suspected human carcinogens present in chlorinated drinking water. Previous studies have shown that many THMs induce sister chromatid exchanges and DNA strand breaks in human peripheral blood lymphocyte...</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2014-title40-vol32/pdf/CFR-2014-title40-vol32-sec798-5375.pdf','CFR2014'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2014-title40-vol32/pdf/CFR-2014-title40-vol32-sec798-5375.pdf"><span>40 CFR 798.5375 - In vitro mammalian cytogenetics.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2014&page.go=Go">Code of Federal Regulations, 2014 CFR</a></p>
<p></p>
<p>2014-07-01</p>
<p>... mammalian cytogenetics. (a) Purpose. The in vitro cytogenetics test is a mutagenicity test system for the... first post-treatment mitosis and numerical aberrations require at least one cell division to be... chromatids. (c) Reference substances. Not applicable. (d) Test method—(1) Principle. In vitro cytogenetics...</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=38455&Lab=NHEERL&keyword=bone&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50','EPA-EIMS'); return false;" href="https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=38455&Lab=NHEERL&keyword=bone&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50"><span>CYTOGENETIC ANALYSES OF MICE EXPOSED TO DICHLOROMETHANE</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://oaspub.epa.gov/eims/query.page">EPA Science Inventory</a></p>
<p></p>
<p></p>
<p>Chromosome damage was studied in female B6C3F1 mice exposed to dichloromethane (DCM) by subcutaneous or inhalation treatments. o increase in either the frequencies of sister chromatid exchanges (SCEs) or chromosome aberrations (CAs) in bone marrow cells was observed after a singl...</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://eric.ed.gov/?q=DNA&pg=6&id=EJ939031','ERIC'); return false;" href="https://eric.ed.gov/?q=DNA&pg=6&id=EJ939031"><span>Chromonoodles: Jump into the Gene Pool</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p>
<p>Farrar, Jennifer; Barnhart, Kelsi</p>
<p>2011-01-01</p>
<p>Chromosomes, alleles, chromatids, genotype, phenotype, mitosis, meiosis, fertilization--this vocabulary can be overwhelming, confusing, and difficult for students to tie together. However, since these terms are commonplace in the high school biology classroom, and are the basis for understanding both DNA and heredity, students must understand…</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27737959','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27737959"><span>Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Martin, Carol-Anne; Murray, Jennie E; Carroll, Paula; Leitch, Andrea; Mackenzie, Karen J; Halachev, Mihail; Fetit, Ahmed E; Keith, Charlotte; Bicknell, Louise S; Fluteau, Adeline; Gautier, Philippe; Hall, Emma A; Joss, Shelagh; Soares, Gabriela; Silva, João; Bober, Michael B; Duker, Angela; Wise, Carol A; Quigley, Alan J; Phadke, Shubha R; Wood, Andrew J; Vagnarelli, Paola; Jackson, Andrew P</p>
<p>2016-10-01</p>
<p>Compaction of chromosomes is essential for accurate segregation of the genome during mitosis. In vertebrates, two condensin complexes ensure timely chromosome condensation, sister chromatid disentanglement, and maintenance of mitotic chromosome structure. Here, we report that biallelic mutations in NCAPD2, NCAPH, or NCAPD3, encoding subunits of these complexes, cause microcephaly. In addition, hypomorphic Ncaph2 mice have significantly reduced brain size, with frequent anaphase chromatin bridge formation observed in apical neural progenitors during neurogenesis. Such DNA bridges also arise in condensin-deficient patient cells, where they are the consequence of failed sister chromatid disentanglement during chromosome compaction. This results in chromosome segregation errors, leading to micronucleus formation and increased aneuploidy in daughter cells. These findings establish "condensinopathies" as microcephalic disorders, with decatenation failure as an additional disease mechanism for microcephaly, implicating mitotic chromosome condensation as a key process ensuring mammalian cerebral cortex size. © 2016 Martin et al.; Published by Cold Spring Harbor Laboratory Press.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5640152','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5640152"><span>Structural maintenance of chromosome complexes differentially compact mitotic chromosomes according to genomic context</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Schalbetter, S. A.; Goloborodko, A.; Fudenberg, G.; Belton, J.-M.; Miles, C.; Yu, M.; Dekker, J.; Mirny, L.; Baxter, J.</p>
<p>2017-01-01</p>
<p>Structural Maintenance of Chromosomes (SMC) protein complexes are key determinants of chromosome conformation. Using Hi-C and polymer modeling, we study how cohesin and condensin, two deeply conserved SMC complexes, organize chromosomes in the budding yeast Saccharomyces cerevisiae. The canonical role of cohesin is to co-align sister chromatids whilst condensin generally compacts mitotic chromosomes. We find strikingly different roles for the two complexes in budding yeast mitosis. First, cohesin is responsible for compacting mitotic chromosome arms, independently of sister chromatid cohesion. Polymer simulations demonstrate this role can be fully accounted for through cis-looping of chromatin. Second, condensin is generally dispensable for compaction along chromosome arms. Instead it plays a targeted role compacting the rDNA proximal regions and promoting resolution of peri-centromeric regions. Our results argue that the conserved mechanism of SMC complexes is to form chromatin loops and that distinct SMC-dependent looping activities are selectively deployed to appropriately compact chromosomes. PMID:28825700</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19002846','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19002846"><span>The effects of boric acid on sister chromatid exchanges and chromosome aberrations in cultured human lymphocytes.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Arslan, Mehmet; Topaktas, Mehmet; Rencuzogullari, Eyyüp</p>
<p>2008-02-01</p>
<p>The aim of this study was to determine the possible genotoxic effects of boric acid (BA) (E284), which is used as an antimicrobial agent in food, by using sister chromatid exchange (SCEs) and chromosome aberration (CAs) tests in human peripheral lymphocytes. The human lymphocytes were treated with 400, 600, 800, and 1000 mug/mL concentrations of BA dissolved in dimethyl sulfoxide (DMSO), for 24 h and 48 h treatment periods. BA did not increase the SCEs for all the concentrations and treatment periods when compared to control and solvent control (DMSO). BA induced structural and total CAs at all the tested concentrations for 24 and 48 h treatment periods. The induction of the total CAs was dose dependent for the 24 h treatment period. However, BA did not cause numerical CAs. BA showed a cytotoxic effect by decreasing the replication index (RI) and mitotic index (MI). BA decreased the MI in a dose-dependent manner for the 24 h treatment period.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4382745','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4382745"><span>Meiosis and Maternal Aging: Insights from Aneuploid Oocytes and Trisomy Births</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Herbert, Mary; Kalleas, Dimitrios; Cooney, Daniel; Lamb, Mahdi; Lister, Lisa</p>
<p>2015-01-01</p>
<p>In most organisms, genome haploidization requires reciprocal DNA exchanges (crossovers) between replicated parental homologs to form bivalent chromosomes. These are resolved to their four constituent chromatids during two meiotic divisions. In female mammals, bivalents are formed during fetal life and remain intact until shortly before ovulation. Extending this period beyond ∼35 years greatly increases the risk of aneuploidy in human oocytes, resulting in a dramatic increase in infertility, miscarriage, and birth defects, most notably trisomy 21. Bivalent chromosomes are stabilized by cohesion between sister chromatids, which is mediated by the cohesin complex. In mouse oocytes, cohesin becomes depleted from chromosomes during female aging. Consistent with this, premature loss of centromeric cohesion is a major source of aneuploidy in oocytes from older women. Here, we propose a mechanistic framework to reconcile data from genetic studies on human trisomy and oocytes with recent advances in our understanding of the molecular mechanisms of chromosome segregation during meiosis in model organisms. PMID:25833844</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25601756','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25601756"><span>Interdependence of the rad50 hook and globular domain functions.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Hohl, Marcel; Kochańczyk, Tomasz; Tous, Cristina; Aguilera, Andrés; Krężel, Artur; Petrini, John H J</p>
<p>2015-02-05</p>
<p>Rad50 contains a conserved Zn(2+) coordination domain (the Rad50 hook) that functions as a homodimerization interface. Hook ablation phenocopies Rad50 deficiency in all respects. Here, we focused on rad50 mutations flanking the Zn(2+)-coordinating hook cysteines. These mutants impaired hook-mediated dimerization, but recombination between sister chromatids was largely unaffected. This may reflect that cohesin-mediated sister chromatid interactions are sufficient for double-strand break repair. However, Mre11 complex functions specified by the globular domain, including Tel1 (ATM) activation, nonhomologous end joining, and DNA double-strand break end resection were affected, suggesting that dimerization exerts a broad influence on Mre11 complex function. These phenotypes were suppressed by mutations within the coiled-coil and globular ATPase domains, suggesting a model in which conformational changes in the hook and globular domains are transmitted via the extended coils of Rad50. We propose that transmission of spatial information in this manner underlies the regulation of Mre11 complex functions. Copyright © 2015 Elsevier Inc. All rights reserved.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22732496','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22732496"><span>Shugoshins function as a guardian for chromosomal stability in nuclear division.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Yao, Yixin; Dai, Wei</p>
<p>2012-07-15</p>
<p>Accurate chromosome segregation during mitosis and meiosis is regulated and secured by several distinctly different yet intricately connected regulatory mechanisms. As chromosomal instability is a hallmark of a majority of tumors as well as a cause of infertility for germ cells, extensive research in the past has focused on the identification and characterization of molecular components that are crucial for faithful chromosome segregation during cell division. Shugoshins, including Sgo1 and Sgo2, are evolutionarily conserved proteins that function to protect sister chromatid cohesion, thus ensuring chromosomal stability during mitosis and meiosis in eukaryotes. Recent studies reveal that Shugoshins in higher animals play an essential role not only in protecting centromeric cohesion of sister chromatids and assisting bi-orientation attachment at the kinetochores, but also in safeguarding centriole cohesion/engagement during early mitosis. Many molecular components have been identified that play essential roles in modulating/mediating Sgo functions. This review primarily summarizes recent advances on the mechanisms of action of Shugoshins in suppressing chromosomal instability during nuclear division in eukaryotic organisms.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/8175058','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/8175058"><span>[Cytogenetic examinations in biomonitoring residents residing closest to the area near the Sendzimir metallurgy plant in Krakow exposed to environmental pollution].</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Kubiak, R; Rudek, Z; Cieszkowski, J; Garlicki, S</p>
<p>1993-01-01</p>
<p>There are many studies done to identify the genetic hazard from occupational exposure of workers, but rather little is known about genetic effects in inhabitants of polluted areas. The aim of the study was to examine chromosome aberrations, sister chromatid exchanges and number of micronuclei in lymphocytes of persons living in the close vicinity of a large metallurgical plant. The results were compared with those obtained for the inhabitants of a village located 40 km from the city of Cracow and from the plant. An increased incidence of chromosome aberrations (0.66-4.66%, control 0.78%), sister chromatid exchanges (mean 9.73, control: 6.0) was found in the group living near the steel foundry. The paper also includes some data on measurements of the air pollution in the Nowa Huta region as well as on the amounts of heavy metals in vegetables in this region. Environmental pollution is worsening.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2011-title40-vol16/pdf/CFR-2011-title40-vol16-sec79-65.pdf','CFR2011'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2011-title40-vol16/pdf/CFR-2011-title40-vol16-sec79-65.pdf"><span>40 CFR 79.65 - In vivo sister chromatid exchange assay.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2011&page.go=Go">Code of Federal Regulations, 2011 CFR</a></p>
<p></p>
<p>2011-07-01</p>
<p>... least five female and five male animals per experimental and control group shall be used. The use of a single sex or different number of animals shall be justified. (5) Positive control group. A single... making comparisons between treated and control groups. (2) Statistical evaluation. Data shall be...</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2013-title40-vol17/pdf/CFR-2013-title40-vol17-sec79-65.pdf','CFR2013'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2013-title40-vol17/pdf/CFR-2013-title40-vol17-sec79-65.pdf"><span>40 CFR 79.65 - In vivo sister chromatid exchange assay.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2013&page.go=Go">Code of Federal Regulations, 2013 CFR</a></p>
<p></p>
<p>2013-07-01</p>
<p>... least five female and five male animals per experimental and control group shall be used. The use of a single sex or different number of animals shall be justified. (5) Positive control group. A single... making comparisons between treated and control groups. (2) Statistical evaluation. Data shall be...</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2014-title40-vol17/pdf/CFR-2014-title40-vol17-sec79-65.pdf','CFR2014'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2014-title40-vol17/pdf/CFR-2014-title40-vol17-sec79-65.pdf"><span>40 CFR 79.65 - In vivo sister chromatid exchange assay.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2014&page.go=Go">Code of Federal Regulations, 2014 CFR</a></p>
<p></p>
<p>2014-07-01</p>
<p>... least five female and five male animals per experimental and control group shall be used. The use of a single sex or different number of animals shall be justified. (5) Positive control group. A single... making comparisons between treated and control groups. (2) Statistical evaluation. Data shall be...</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol16/pdf/CFR-2010-title40-vol16-sec79-65.pdf','CFR'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol16/pdf/CFR-2010-title40-vol16-sec79-65.pdf"><span>40 CFR 79.65 - In vivo sister chromatid exchange assay.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2010&page.go=Go">Code of Federal Regulations, 2010 CFR</a></p>
<p></p>
<p>2010-07-01</p>
<p>... least five female and five male animals per experimental and control group shall be used. The use of a single sex or different number of animals shall be justified. (5) Positive control group. A single... making comparisons between treated and control groups. (2) Statistical evaluation. Data shall be...</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2012-title40-vol17/pdf/CFR-2012-title40-vol17-sec79-65.pdf','CFR2012'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2012-title40-vol17/pdf/CFR-2012-title40-vol17-sec79-65.pdf"><span>40 CFR 79.65 - In vivo sister chromatid exchange assay.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2012&page.go=Go">Code of Federal Regulations, 2012 CFR</a></p>
<p></p>
<p>2012-07-01</p>
<p>... least five female and five male animals per experimental and control group shall be used. The use of a single sex or different number of animals shall be justified. (5) Positive control group. A single... making comparisons between treated and control groups. (2) Statistical evaluation. Data shall be...</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24444548','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24444548"><span>Sister chromatid exchange, (SCE), High-Frequency Cells (HFCs) and SCE distribution patterns in peripheral blood lymphocytes of Spanish adult smokers compared to non-smokers.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Sebastià, Natividad; Hervás, David; Almonacid, Miguel; Villaescusa, Juan Ignacio; Soriano, José Miguel; Sahuquillo, Vicenta; Esteban, Valentín; Barquinero, Joan Francesc; Verdú, Gumersindo; Cervera, José; Such, Esperanza; Montoro, Alegría</p>
<p>2014-04-01</p>
<p>According to the International Agency for Research on Cancer, smoking tobacco is a major cause of cancer in humans. It causes about half of all male cancer deaths and an ever increasing number of cancer deaths in females. The aim of this study was to establish whether cigarette smoking increases sister chromatid exchanges (SCEs) in peripheral blood lymphocytes in two Spanish population groups; light and heavy smokers. The mean number of High-Frequency Cells (HFCs) was determined and, the SCE distribution pattern among the chromosomes was analysed represented by a ratio described below. A local sample of 101 adult smokers (n=48) and non-smokers (n=53), aged from 18 to 49 years, was studied using SCE levels in peripheral lymphocytes. Heavy smoking (≥ 10 cigarettes per day) increased significantly the SCE frequency and the HFC parameters. Neither age nor sex significantly influenced the frequencies in the groups studied. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/15024062','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/15024062"><span>Securin is a target of the UV response pathway in mammalian cells.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Romero, Francisco; Gil-Bernabé, Ana M; Sáez, Carmen; Japón, Miguel A; Pintor-Toro, José A; Tortolero, María</p>
<p>2004-04-01</p>
<p>All eukaryotic cells possess elaborate mechanisms to protect genome integrity and ensure survival after DNA damage, ceasing proliferation and granting time for DNA repair. Securin is an inhibitory protein that is bound to a protease called Separase to inhibit sister chromatid separation until the onset of anaphase. At the metaphase-to-anaphase transition, Securin is degraded by the anaphase-promoting complex or cyclosome, and Separase contributes to the release of cohesins from the chromosome, allowing for the segregation of sister chromatids to opposite spindle poles. Here we provide evidence that human Securin (hSecurin) has a novel role in cell cycle arrest after exposure to UV light or ionizing radiation. In fact, irradiation downregulated the level of hSecurin protein, accelerating its degradation via the proteasome and reducing hSecurin mRNA translation, but the presence of hSecurin is necessary for cell proliferation arrest following UV treatment. Moreover, an alteration of UV-induced hSecurin downregulation could lead directly to the accumulation of DNA damage and the subsequent development of malignant tumors.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=371137','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=371137"><span>Securin Is a Target of the UV Response Pathway in Mammalian Cells†</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Romero, Francisco; Gil-Bernabé, Ana M.; Sáez, Carmen; Japón, Miguel A.; Pintor-Toro, José A.; Tortolero, María</p>
<p>2004-01-01</p>
<p>All eukaryotic cells possess elaborate mechanisms to protect genome integrity and ensure survival after DNA damage, ceasing proliferation and granting time for DNA repair. Securin is an inhibitory protein that is bound to a protease called Separase to inhibit sister chromatid separation until the onset of anaphase. At the metaphase-to-anaphase transition, Securin is degraded by the anaphase-promoting complex or cyclosome, and Separase contributes to the release of cohesins from the chromosome, allowing for the segregation of sister chromatids to opposite spindle poles. Here we provide evidence that human Securin (hSecurin) has a novel role in cell cycle arrest after exposure to UV light or ionizing radiation. In fact, irradiation downregulated the level of hSecurin protein, accelerating its degradation via the proteasome and reducing hSecurin mRNA translation, but the presence of hSecurin is necessary for cell proliferation arrest following UV treatment. Moreover, an alteration of UV-induced hSecurin downregulation could lead directly to the accumulation of DNA damage and the subsequent development of malignant tumors. PMID:15024062</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1684051','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1684051"><span>Chromatid repulsion associated with Roberts/SC phocomelia syndrome is reduced in malignant cells and not expressed in interspecies somatic-cell hybrids.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Krassikoff, N E; Cowan, J M; Parry, D M; Francke, U</p>
<p>1986-01-01</p>
<p>Different cell types from a female patient with Roberts/SC phocomelia syndrome were evaluated quantitatively for the presence of repulsion of heterochromatin and satellite regions of mitotic chromosomes. Whereas EBV-transformed lymphoblasts from an established cell line revealed these phenomena at frequencies equal to those in PHA-stimulated lymphocytes and cultured skin fibroblasts, aneuploid cells from a metastatic melanoma displayed them at 50% lower frequency. Cocultivation of the patient's fibroblasts with either an immortal Chinese hamster cell line or with a human male fibroblast strain carrying a t(4;6)(p14;q21) translocation showed that the phenomenon was not corrected or induced by a diffusible factor or by cell-to-cell contact. In each experiment, only the patient's metaphase spreads revealed chromatid repulsion. In fusion hybrids between the patient's fibroblasts and an established Chinese hamster cell line, the human chromosomes behaved perfectly normally, suggesting that the gene product which is missing or mutant in Roberts/SC phocomelia syndrome is supplied by the Chinese hamster genome. Images Fig. 1 Fig. 2 Fig. 3 PMID:3788975</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/15797924','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/15797924"><span>Mitomycin C-induced pairing of heterochromatin reflects initiation of DNA repair and chromatid exchange formation.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Abdel-Halim, H I; Natarajan, A T; Mullenders, L H F; Boei, J J W A</p>
<p>2005-04-15</p>
<p>Chromatid interchanges induced by the DNA cross-linking agent mitomycin C (MMC) are over-represented in human chromosomes containing large heterochromatic regions. We found that nearly all exchange breakpoints of chromosome 9 are located within the paracentromeric heterochromatin and over 70% of exchanges involving chromosome 9 are between its homologues. We provide evidence that the required pairing of chromosome 9 heterochromatic regions occurs in G(0)/G(1) and S-phase cells as a result of an active cellular process initiated upon MMC treatment. By contrast, no pairing was observed for a euchromatic paracentromeric region of the equal-sized chromosome 8. The MMC-induced pairing of chromosome 9 heterochromatin is observed in a subset of cells; its percentage closely mimics the frequency of homologous interchanges found at metaphase. Moreover, the absence of pairing in cells derived from XPF patients correlates with an altered spectrum of MMC-induced exchanges. Together, the data suggest that the heterochromatin-specific pairing following MMC treatment reflects the initiation of DNA cross-link repair and the formation of exchanges.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2592668','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2592668"><span>Regulation of the Anaphase-promoting Complex–Separase Cascade by Transforming Growth Factor-β Modulates Mitotic Progression in Bone Marrow Stromal Cells</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Fujita, Takeo; Epperly, Michael W.; Zou, Hui; Greenberger, Joel S.</p>
<p>2008-01-01</p>
<p>Alteration of the tumor microenvironment by aberrant stromal cells influences many aspects of cell biology, including differentiation of stem cells and tumor metastasis. The role of transforming growth factor (TGF)-β signaling in stromal cells of the tissue microenvironment is critical to both pathways. We examined murine marrow stromal cells with deletion of Smad3 and found that they have an altered cell cycle profile, with a higher fraction of cells in G2/M phase. Deletion of Smad3 significantly abrogates TGF-β signaling and suppresses phosphorylation of CDC27–anaphase-promoting complex (APC) during mitosis, thereby resulting in elevated cyclin-dependent kinase (CDK)1 activity via increased levels of cyclin B. Enhanced CDK1 activity due to deregulation of APC leads in turn to hyperphosphorylation of separase, impeding chromatid separation. A residue Ser1126Ala mutation in separase specifically abolished separase hyperphosphorylation in Smad3-deficient cells. The present results unveil a new function for the TGF-β pathway in the regulation of APC to mediate chromatid separation during mitosis. PMID:18843049</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11287294','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11287294"><span>Cytogenetic analysis of children under long-term antibacterial therapy with nitroheterocyclic compound furagin.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Slapsyte, G; Jankauskiene, A; Mierauskiene, J; Lazutka, J R</p>
<p>2001-04-05</p>
<p>Cytogenetic analysis of chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) was performed in 109 blood samples from 95 pediatric patients with urinary tract infections (UTIs). Children were exposed to diagnostic levels of X-rays during voiding cystourethrography and subsequently treated for one to 12 months with low doses of furagin - N-(5-nitro-2-furyl)-allylidene-1-aminohydantoin. Furagin is 2-substituted 5-nitrofuran, chemically and structurally similar to well-known antibacterial compound nitrofurantoin. Increased frequencies of CAs were found in children undergoing voiding cystourethrography as compared with the unexposed, acentric fragments being the most frequent alteration (2.03 versus 0.88 per 100 cells, P=0.006). However, a significant decrease in the frequency of acentric fragments was determined with the time elapsed since X-ray examination was performed. A time-independent increase in SCE frequency was found in lymphocytes of children treated with furagin. Total CA frequency did not differ significantly between groups of children with various duration of furagin treatment. However, frequency of chromatid exchanges (triradials and quadriradials) increased significantly with duration of treatment.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4598568','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4598568"><span>Bub1 autophosphorylation feeds back to regulate kinetochore docking and promote localized substrate phosphorylation</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Asghar, Adeel; Lajeunesse, Audrey; Dulla, Kalyan; Combes, Guillaume; Thebault, Philippe; Nigg, Erich A.; Elowe, Sabine</p>
<p>2015-01-01</p>
<p>During mitosis, Bub1 kinase phosphorylates histone H2A-T120 to promote centromere sister chromatid cohesion through recruitment of shugoshin (Sgo) proteins. The regulation and dynamics of H2A-T120 phosphorylation are poorly understood. Using quantitative phosphoproteomics we show that Bub1 is autophosphorylated at numerous sites. We confirm mitosis-specific autophosphorylation of a several residues and show that Bub1 activation is primed in interphase but fully achieved only in mitosis. Mutation of a single autophosphorylation site T589 alters kinetochore turnover of Bub1 and results in uniform H2A-T120 phosphorylation and Sgo recruitment along chromosome arms. Consequently, improper sister chromatid resolution and chromosome segregation errors are observed. Kinetochore tethering of Bub1-T589A refocuses H2A-T120 phosphorylation and Sgo1 to centromeres. Recruitment of the Bub1-Bub3-BubR1 axis to kinetochores has recently been extensively studied. Our data provide novel insight into the regulation and kinetochore residency of Bub1 and indicate that its localization is dynamic and tightly controlled through feedback autophosphorylation. PMID:26399325</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26399325','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26399325"><span>Bub1 autophosphorylation feeds back to regulate kinetochore docking and promote localized substrate phosphorylation.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Asghar, Adeel; Lajeunesse, Audrey; Dulla, Kalyan; Combes, Guillaume; Thebault, Philippe; Nigg, Erich A; Elowe, Sabine</p>
<p>2015-09-24</p>
<p>During mitosis, Bub1 kinase phosphorylates histone H2A-T120 to promote centromere sister chromatid cohesion through recruitment of shugoshin (Sgo) proteins. The regulation and dynamics of H2A-T120 phosphorylation are poorly understood. Using quantitative phosphoproteomics we show that Bub1 is autophosphorylated at numerous sites. We confirm mitosis-specific autophosphorylation of a several residues and show that Bub1 activation is primed in interphase but fully achieved only in mitosis. Mutation of a single autophosphorylation site T589 alters kinetochore turnover of Bub1 and results in uniform H2A-T120 phosphorylation and Sgo recruitment along chromosome arms. Consequently, improper sister chromatid resolution and chromosome segregation errors are observed. Kinetochore tethering of Bub1-T589A refocuses H2A-T120 phosphorylation and Sgo1 to centromeres. Recruitment of the Bub1-Bub3-BubR1 axis to kinetochores has recently been extensively studied. Our data provide novel insight into the regulation and kinetochore residency of Bub1 and indicate that its localization is dynamic and tightly controlled through feedback autophosphorylation.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/8248278','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/8248278"><span>Enhancement of antineoplastic effect and attenuation of sister chromatid exchanges by prostaglandin E2 in Ehrlich ascites tumour cells treated with cyclophosphamide in vivo.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Mourelatos, D; Kritsi, Z; Mioglou, E; Dozi-Vassiliades, J</p>
<p>1993-09-01</p>
<p>Reduced sister chromatid exchanges (SCE) frequency in response to cyclophosphamide (CP) was observed when Ehrlich ascites tumour (EAT) cells were exposed in vivo to 2 micrograms/g body weight of prostaglandin E2 (PGE2). 1 h before i.p. injection of 5-bromodeoxyuridine (BrdUrd) adsorbed to activated charcoal, EAT-bearing mice treated i.p. with CP appeared to have increased SCE rates and cell division delays. PGE2 had no effect on survival and in inhibiting tumour growth. CP had only a slight non-significant effect on survival and in inhibiting tumour growth. In mice treated with the combined CP (5 micrograms/g bd wt) plus PGE2 (2 micrograms/g bd wt) a significant enhancement (P < 0.01) of survival time was accompanied by inhibition of tumour growth (P < 0.01) in comparison with the untreated controls. These data imply that SCEs might result from errors in a repair process which might involve a PGE2 sensitive step.</p>
</li>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/12132876','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/12132876"><span>Comparative study of sister chromatid exchange induction and antitumor effects by homo-aza-steroidal esters of [p-[bis(2-chloroethyl)amino]phenyl]butyric acid.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Camoutsis, C; Catsoulacos, D; Karayiann, V; Papageorgiou, A; Mourelatos, D; Mioglou, E; Kritsi, Z; Nikolaropoulos, S</p>
<p>2001-01-01</p>
<p>The present work was undertaken in order to test the hypothesis that the Sister Chromatid Exchange (SCE) assay in vitro can be used for the prediction of in vivo tumor response to newly synthesized potential chemotherapeutics. The effect of three homo-aza-steroidal esters containing the -CONH- in the steroidal nucleus, 1, 2, and 3 on SCE rates and on cell kinetics in cultured human lymphocytes was studied. The antitumor activity of these compounds was tested on leukemia P388- and leukemia L1210-bearing mice. The three substances induced statistically significant enhancement of SCEs and of cell division delays. Compounds 1 and 3 were identified, on a molar basis, as more effective inducers of SCEs and of cell division delays compared with compound 2. Compounds 1 and 3 had upon both experimental tumors better therapeutic effects compared with compound 2 at equitoxic doses. Therefore, the order of the antitumor effectiveness of the three compounds coincided with the order of the cytogenetic effects they induced.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2715236','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2715236"><span>The Walker B motif in avian FANCM is required to limit sister chromatid exchanges but is dispensable for DNA crosslink repair</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Rosado, Ivan V.; Niedzwiedz, Wojciech; Alpi, Arno F.; Patel, Ketan J.</p>
<p>2009-01-01</p>
<p>FANCM, the most highly conserved component of the Fanconi Anaemia (FA) pathway can resolve recombination intermediates and remodel synthetic replication forks. However, it is not known if these activities are relevant to how this conserved protein activates the FA pathway and promotes DNA crosslink repair. Here we use chicken DT40 cells to systematically dissect the function of the helicase and nuclease domains of FANCM. Our studies reveal that these domains contribute distinct roles in the tolerance of crosslinker, UV light and camptothecin-induced DNA damage. Although the complete helicase domain is critical for crosslink repair, a predicted inactivating mutation of the Walker B box domain has no impact on FA pathway associated functions. However, this mutation does result in elevated sister chromatid exchanges (SCE). Furthermore, our genetic dissection indicates that FANCM functions with the Blm helicase to suppress spontaneous SCE events. Overall our results lead us to reappraise the role of helicase domain associated activities of FANCM with respect to the activation of the FA pathway, crosslink repair and in the resolution of recombination intermediates. PMID:19465393</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29760389','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29760389"><span>Aurora A-dependent CENP-A phosphorylation at inner centromeres protects bioriented chromosomes against cohesion fatigue.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Eot-Houllier, Grégory; Magnaghi-Jaulin, Laura; Fulcrand, Géraldine; Moyroud, François-Xavier; Monier, Solange; Jaulin, Christian</p>
<p>2018-05-14</p>
<p>Sustained spindle tension applied to sister centromeres during mitosis eventually leads to uncoordinated loss of sister chromatid cohesion, a phenomenon known as "cohesion fatigue." We report that Aurora A-dependent phosphorylation of serine 7 of the centromere histone variant CENP-A (p-CENP-AS7) protects bioriented chromosomes against cohesion fatigue. Expression of a non-phosphorylatable version of CENP-A (CENP-AS7A) weakens sister chromatid cohesion only when sister centromeres are under tension, providing the first evidence of a regulated mechanism involved in protection against passive cohesion loss. Consistent with this observation, p-CENP-AS7 is detected at the inner centromere where it forms a discrete domain. The depletion or inhibition of Aurora A phenocopies the expression of CENP-AS7A and we show that Aurora A is recruited to centromeres in a Bub1-dependent manner. We propose that Aurora A-dependent phosphorylation of CENP-A at the inner centromere protects chromosomes against tension-induced cohesion fatigue until the last kinetochore is attached to spindle microtubules.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29804664','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29804664"><span>Assays for the spindle assembly checkpoint in cell culture.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Marcozzi, Chiara; Pines, Jonathon</p>
<p>2018-01-01</p>
<p>The spindle assembly checkpoint (SAC) is crucial to maintain genomic stability since it prevents premature separation of sister chromatids in mitosis and ensures the fidelity of chromosome segregation. The SAC arrests cells in mitosis and is not satisfied until all kinetochores are stably attached to the mitotic spindle. Improperly attached kinetochores activate the SAC and catalyze the formation of the mitotic checkpoint complex (MCC), containing Mad2, Cdc20, BubR1, and Bub3 proteins. The MCC binds and thereby inhibits the APC/C E3 ubiquitin ligase until the last kinetochore has attached to microtubules. Once the SAC is satisfied, the APC/C promptly activates and targets cyclin B1 and securin for degradation, thus allowing sister chromatids to separate and the cell to exit mitosis. Our understanding of SAC signaling has increased thanks to the development of new genetic, biochemical, molecular, and structural biology techniques. Here, we describe how live-cell imaging microscopy in combination with gene-targeting strategies and biochemical assays can be exploited to investigate the intrinsic properties of the SAC in mammalian cultured cells. © 2018 Elsevier Inc. All rights reserved.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/10390512','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/10390512"><span>Induction and prevention of micronuclei and chromosomal aberrations in cultured human lymphocytes exposed to the light of halogen tungsten lamps.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>D'Agostini, F; Caimo, A; De Filippi, S; De Flora, S</p>
<p>1999-07-01</p>
<p>Previous studies have shown that the light emitted by halogen tungsten lamps contains UV radiation in the UV-A, UV-B and UV-C regions, induces mutations and irreparable DNA damage in bacteria, enhances the frequency of micronuclei in cultured human lymphocytes and is potently carcinogenic to the skin of hairless mice. The present study showed that the light emitted by an uncovered, traditional halogen lamp induces a significant, dose-related and time-related increase not only in micronuclei but also in chromosome-type aberrations, such as breaks, and even more in chromatid-type aberrations, such as isochromatid breaks, exchanges and isochromatid/chromatid interchanges, all including gaps or not, in cultured human lymphocytes. All these genotoxic effects were completely prevented by shielding the same lamp with a silica glass cover, blocking UV radiation. A new model of halogen lamp, having the quartz bulb treated in order to reduce the output of UV radiation, was considerably less genotoxic than the uncovered halogen lamp, yet induction of chromosomal alterations was observed at high illuminance levels.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1202954','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1202954"><span>One-Step and Stepwise Magnification of a BOBBED LETHAL Chromosome in DROSOPHILA MELANOGASTER</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Endow, Sharyn A.; Komma, Donald J.</p>
<p>1986-01-01</p>
<p>Bobbed lethal (bbl) chromosomes carry too few ribosomal genes for homozygous flies to be viable. Reversion of bbl chromosomes to bb or nearly bb + occurs under magnifying conditions at a low frequency in a single generation. These reversions occur too rapidly to be accounted for by single unequal sister chromatid exchanges and seem unlikely to be due to multiple sister strand exchanges within a given cell lineage. Analysis of several one-step revertants indicates that they are X-Y recombinant chromosomes which probably arise from X-Y recombination at bb. The addition of ribosomal genes from the Y chromosome to the bbl chromosome explains the more rapid reversion of the bbl chromosome than is permitted by single events of unequal sister chromatid exchange. Analysis of stepwise bbl magnified chromosomes, which were selected over a period of 4–9 magnifying generations, shows ribosomal gene patterns that are closely similar to each other. Similarity in rDNA pattern among stepwise magnified products of the same parental chromosome is consistent with reversion by a mechanism of unequal sister strand exchange. PMID:3095184</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/16737721','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/16737721"><span>Loss of heterozygosity in yeast can occur by ultraviolet irradiation during the S phase of the cell cycle.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Daigaku, Yasukazu; Mashiko, Satsuki; Mishiba, Keiichiro; Yamamura, Saburo; Ui, Ayako; Enomoto, Takemi; Yamamoto, Kazuo</p>
<p>2006-08-30</p>
<p>A CAN1/can1Delta heterozygous allele that determines loss of heterozygosity (LOH) was used to study recombination in Saccharomyces cerevisiae cells exposed to ultraviolet (UV) light at different points in the cell cycle. With this allele, recombination events can be detected as canavanine-resistant mutations after exposure of cells to UV radiation, since a significant fraction of LOH events appear to arise from recombination between homologous chromosomes. The radiation caused a higher level of LOH in cells that were in the S phase of the cell cycle relative to either cells at other points in the cell cycle or unsynchronized cells. In contrast, the inactivation of nucleotide excision repair abolished the cell cycle-specific induction by UV of LOH. We hypothesize that DNA lesions, if not repaired, were converted into double-strand breaks during stalled replication and these breaks could be repaired through recombination using a non-sister chromatid and probably also the sister chromatid. We argue that LOH may be an outcome used by yeast cells to recover from stalled replication at a lesion.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2032657','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2032657"><span>Relationship of Chromosome Changes to Neoplastic Cell Transformation</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>DiPaolo, Joseph A.; Popescu, Nicolae C.</p>
<p>1976-01-01</p>
<p>Chromosomal abnormalities are a frequent concomitant of neoplasia, and although it is tempting to relate these mutations and alterations in chromatin (DNA) function to cancer, their relationship to the initiation or progression of carcinogenesis is unknown. Mammalian cells in culture, after interacting with chemical carcinogens, often exhibit chromosome damage consisting of breaks and exchanges of chromatid material. The pattern of damage of banded metaphases indicates that negative bands are especially vulnerable to the action of chemical carcinogens, probably because of differential chromatin condensation. Damage to individual chromosomes may be random or nonrandom, depending on the species. Cell death can be correlated with chromatid alterations that occur shortly after treatment with chemical carcinogens. There is also a correlation between mutagenic and carcinogenic activity of some chemical carcinogens and the frequency of sister chromatid exchanges. The question of whether specific chromosome changes are absolutely required for neoplastic transformation cannot be answered because of conflicting data and diverse results from studies even with known carcinogens. Cell transformation may occur without any visible chromosome changes. A universal specific numerical or visible structural chromosomal alteration is not necessarily associated with chemical or viral transformation. Chromosome changes are independent of the etiologic agents: different carcinogens may produce transformation associated with the same abnormal chromosomes, but not all transformed lines invariably exhibit the same abnormality, even with the same chemical. In some species, chromosome having nucleolar organizer regions may be more frequently involved in numerical or structural deviations. Progressively growing tumors also may occur as a result of the proliferation of transformed cells without detectable chromosome changes, indicating that tumorigenicity need not be related to an imbalance of chromosome number or structure. Our studies indicate that chromosome changes are not essential for establishment of neoplasms but that karyotypic instability may result in response to selective growth pressures. ImagesFigure 2Figure 11Figure 3Figure 12Figure 4Figure 5Figure 6Figure 7Figure 8Figure 9Figure 1Figure 10 PMID:826168</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('http://www.ars.usda.gov/research/publications/publication/?seqNo115=325302','TEKTRAN'); return false;" href="http://www.ars.usda.gov/research/publications/publication/?seqNo115=325302"><span>Germplasm enhancement of maize: A look into haploid induction and chromosomal doubling of haploids from temperate-adapted tropical sources</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ars.usda.gov/research/publications/find-a-publication/">USDA-ARS?s Scientific Manuscript database</a></p>
<p></p>
<p></p>
<p>Doubled haploid technology is used to develop completely homozygous inbred lines, where each of the chromatids making up a chromosome pair are identical. Two inbred lines, PHB47 and PHZ51, were used to make backcrosses to 18 maize landraces, generating 36 populations. The landraces were chosen bas...</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://eric.ed.gov/?q=mitosis&pg=2&id=EJ847053','ERIC'); return false;" href="https://eric.ed.gov/?q=mitosis&pg=2&id=EJ847053"><span>Using Long-Term Time-Lapse Imaging of Mammalian Cell Cycle Progression for Laboratory Instruction and Analysis</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p>
<p>Hinchcliffe, Edward H.</p>
<p>2005-01-01</p>
<p>Cinemicrography--the capture of moving cellular sequences through the microscope--has been influential in revealing the dynamic nature of cellular behavior. One of the more dramatic cellular events is mitosis, the division of sister chromatids into two daughter cells. Mitosis has been extensively studied in a variety of organisms, both…</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=48048&Lab=ORD&keyword=bone&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50','EPA-EIMS'); return false;" href="https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=48048&Lab=ORD&keyword=bone&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50"><span>KINETICS OF IN VIVO SISTER CHROMATID EXCHANGE INDUCTION IN MOUSE BONE MARROW CELLS IN ETHYLNITROSOUREA AND METHYLNITROSOUREA</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://oaspub.epa.gov/eims/query.page">EPA Science Inventory</a></p>
<p></p>
<p></p>
<p>Administration of ethylnitrosourea (ENU) (20, 25, 40, 50, and 60 mg/kg body weight) or methylnitrosourea (MNU) (25, 40, 50, 60, 75, and 80 mg/kg body weight) to male CD-1 mice 2 hours after subcutaneous implantation of 5-bromo-2'-deoxyurdine (BrdUrd) pellet (55 mg) resulted in a ...</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11139603','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11139603"><span>Termini of human chromosomes display elevated rates of mitotic recombination.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Cornforth, M N; Eberle, R L</p>
<p>2001-01-01</p>
<p>The strand-specific in situ hybridization technique of CO-FISH was used to probe telomeres of human mitotic cells in order to determine the spontaneous frequency of crossover. This approach allowed the detection of recombinational crossovers occurring anywhere along the length of individual chromosomes, including reciprocal events taking place between sister chromatids. Although the process of sister chromatid exchange (SCE) is the most prominent type of recombination in somatic mammalian cells, our results show that SCEs accounted for less than a third of the recombinational events revealed by CO-FISH. It is concluded that chromosomal regions near the termini of chromosome arms undergo extraordinarily high rates of spontaneous recombination, producing terminal crossovers whose small size precludes detection by standard cytogenetic methods. That similar results were observed for transformed epithelial cells, as well as primary fibroblasts, suggests that the phenomenon is a common characteristic of human cells. These findings are noteworthy because, although telomeric and subtelomeric DNA is known to be preferentially involved in certain types of recombination, the tips of somatic mammalian chromosomes have not previously been identified as preferred sites for crossover. Implications of these results are discussed in terms of limitations imposed on CO-FISH for its proposed use in directional hybridization mapping.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2846563','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2846563"><span>Chromosomal instability in the lymphocytes of breast cancer patients</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Harsimran, Kaur; Kaur, Monga Gaganpreet; Nitika, Setia; Meena, Sudan; M. S., Uppal; Yamini; A. P. S., Batra; Vasudha, Sambyal</p>
<p>2009-01-01</p>
<p>Genomic instability in the tumor tissue has been correlated with tumor progression. In the present study, chromosomal aberrations (CAs) in peripheral blood lymphocytes (PBLs) of breast tumor patients were studied to assess whether chromosomal instability (CIN) in PBLs correlates with aggressiveness of breast tumor (i.e., disease stage) and has any prognostic utility. Cultured blood lymphocyte metaphases were scored for aberrations in 31 breast cancer patients and 20 healthy age and sex-matched controls. A variety of CAs, including aneuploidy, polyploidy, terminal deletions, acentric fragments, double minutes, chromatid separations, ring chromosome, marker chromosome, chromatid gaps, and breaks were seen in PBLs of the patients. The CAs in patients were higher than in controls. A comparison of the frequency of metaphases with aberrations by grouping the patients according to the stage of advancement of disease did not reveal any consistent pattern of variation in lymphocytic CIN. Neither was any specific chromosomal abnormality found to be associated with the stage of cancer. This might be indicative of the fact that cancer patients have constitutional CIN, which predisposes them to the disease, and this inherent difference in the level of genomic instability might play a role in disease progression and response to treatment. PMID:20407644</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3374747','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3374747"><span>Spindle checkpoint–independent inhibition of mitotic chromosome segregation by Drosophila Mps1</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Althoff, Friederike; Karess, Roger E.; Lehner, Christian F.</p>
<p>2012-01-01</p>
<p>Monopolar spindle 1 (Mps1) is essential for the spindle assembly checkpoint (SAC), which prevents anaphase onset in the presence of misaligned chromosomes. Moreover, Mps1 kinase contributes in a SAC-independent manner to the correction of erroneous initial attachments of chromosomes to the spindle. Our characterization of the Drosophila homologue reveals yet another SAC-independent role. As in yeast, modest overexpression of Drosophila Mps1 is sufficient to delay progression through mitosis during metaphase, even though chromosome congression and metaphase alignment do not appear to be affected. This delay in metaphase depends on the SAC component Mad2. Although Mps1 overexpression in mad2 mutants no longer causes a metaphase delay, it perturbs anaphase. Sister kinetochores barely move apart toward spindle poles. However, kinetochore movements can be restored experimentally by separase-independent resolution of sister chromatid cohesion. We propose therefore that Mps1 inhibits sister chromatid separation in a SAC-independent manner. Moreover, we report unexpected results concerning the requirement of Mps1 dimerization and kinase activity for its kinetochore localization in Drosophila. These findings further expand Mps1's significance for faithful mitotic chromosome segregation and emphasize the importance of its careful regulation. PMID:22553353</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22553353','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22553353"><span>Spindle checkpoint-independent inhibition of mitotic chromosome segregation by Drosophila Mps1.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Althoff, Friederike; Karess, Roger E; Lehner, Christian F</p>
<p>2012-06-01</p>
<p>Monopolar spindle 1 (Mps1) is essential for the spindle assembly checkpoint (SAC), which prevents anaphase onset in the presence of misaligned chromosomes. Moreover, Mps1 kinase contributes in a SAC-independent manner to the correction of erroneous initial attachments of chromosomes to the spindle. Our characterization of the Drosophila homologue reveals yet another SAC-independent role. As in yeast, modest overexpression of Drosophila Mps1 is sufficient to delay progression through mitosis during metaphase, even though chromosome congression and metaphase alignment do not appear to be affected. This delay in metaphase depends on the SAC component Mad2. Although Mps1 overexpression in mad2 mutants no longer causes a metaphase delay, it perturbs anaphase. Sister kinetochores barely move apart toward spindle poles. However, kinetochore movements can be restored experimentally by separase-independent resolution of sister chromatid cohesion. We propose therefore that Mps1 inhibits sister chromatid separation in a SAC-independent manner. Moreover, we report unexpected results concerning the requirement of Mps1 dimerization and kinase activity for its kinetochore localization in Drosophila. These findings further expand Mps1's significance for faithful mitotic chromosome segregation and emphasize the importance of its careful regulation.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28590163','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28590163"><span>Merotelic kinetochore attachment in oocyte meiosis II causes sister chromatids segregation errors in aged mice.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Cheng, Jin-Mei; Li, Jian; Tang, Ji-Xin; Hao, Xiao-Xia; Wang, Zhi-Peng; Sun, Tie-Cheng; Wang, Xiu-Xia; Zhang, Yan; Chen, Su-Ren; Liu, Yi-Xun</p>
<p>2017-08-03</p>
<p>Mammalian oocyte chromosomes undergo 2 meiotic divisions to generate haploid gametes. The frequency of chromosome segregation errors during meiosis I increase with age. However, little attention has been paid to the question of how aging affects sister chromatid segregation during oocyte meiosis II. More importantly, how aneuploid metaphase II (MII) oocytes from aged mice evade the spindle assembly checkpoint (SAC) mechanism to complete later meiosis II to form aneuploid embryos remains unknown. Here, we report that MII oocytes from naturally aged mice exhibited substantial errors in chromosome arrangement and configuration compared with young MII oocytes. Interestingly, these errors in aged oocytes had no impact on anaphase II onset and completion as well as 2-cell formation after parthenogenetic activation. Further study found that merotelic kinetochore attachment occurred more frequently and could stabilize the kinetochore-microtubule interaction to ensure SAC inactivation and anaphase II onset in aged MII oocytes. This orientation could persist largely during anaphase II in aged oocytes, leading to severe chromosome lagging and trailing as well as delay of anaphase II completion. Therefore, merotelic kinetochore attachment in oocyte meiosis II exacerbates age-related genetic instability and is a key source of age-dependent embryo aneuploidy and dysplasia.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2171180','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2171180"><span>Recombination protein Tid1p controls resolution of cohesin-dependent linkages in meiosis in Saccharomyces cerevisiae</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Kateneva, Anna V.; Konovchenko, Anton A.; Guacci, Vincent; Dresser, Michael E.</p>
<p>2005-01-01</p>
<p>Sister chromatid cohesion and interhomologue recombination are coordinated to promote the segregation of homologous chromosomes instead of sister chromatids at the first meiotic division. During meiotic prophase in Saccharomyces cerevisiae, the meiosis-specific cohesin Rec8p localizes along chromosome axes and mediates most of the cohesion. The mitotic cohesin Mcd1p/Scc1p localizes to discrete spots along chromosome arms, and its function is not clear. In cells lacking Tid1p, which is a member of the SWI2/SNF2 family of helicase-like proteins that are involved in chromatin remodeling, Mcd1p and Rec8p persist abnormally through both meiotic divisions, and chromosome segregation fails in the majority of cells. Genetic results indicate that the primary defect in these cells is a failure to resolve Mcd1p-mediated connections. Tid1p interacts with recombination enzymes Dmc1p and Rad51p and has an established role in recombination repair. We propose that Tid1p remodels Mcd1p-mediated cohesion early in meiotic prophase to facilitate interhomologue recombination and the subsequent segregation of homologous chromosomes. PMID:16230461</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17451994','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17451994"><span>Vicia root-mirconucleus and sister chromatid exchange assays on the genotoxicity of selenium compounds.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Yi, Huilan; Si, Liangyan</p>
<p>2007-06-15</p>
<p>Selenium (Se) is an important metalloid with industrial, environmental, biological and toxicological significance. Excessive selenium in soil and water may contribute to environmental selenium pollution, and affect plant growth and human health. By using Vicia faba micronucleus (MN) and sister chromatid exchange (SCE) tests, possible genotoxicity of sodium selenite and sodium biselenite was evaluated in this study. The results showed that sodium selenite, at concentrations from 0.01 to 10.0mg/L, induced a 1.9-3.9-fold increase in MN frequency and a 1.5-1.6-fold increase in SCE frequency, with a statistically significantly difference from the control (P<0.05 and 0.01, respectively). Sodium selenite also caused mitotic delay and a 15-80% decrease in mitotic indices (MI), but at the lowest concentration (0.005mg/L), it slightly stimulated mitotic activity. Similarly, the frequencies of MN and SCE also increased significantly in sodium biselenite treated samples, with MI decline only at relatively higher effective concentrations. Results of the present study suggest that selenite is genotoxic to V. faba root cells and may be a genotoxic risk to human health.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1460327','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1460327"><span>The Saccharomyces cerevisiae RAD9, RAD17, RAD24 and MEC3 genes are required for tolerating irreparable, ultraviolet-induced DNA damage.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Paulovich, A G; Armour, C D; Hartwell, L H</p>
<p>1998-01-01</p>
<p>In wild-type Saccharomyces cerevisiae, a checkpoint slows the rate of progression of an ongoing S phase in response to exposure to a DNA-alkylating agent. Mutations that eliminate S phase regulation also confer sensitivity to alkylating agents, leading us to suggest that, by regulating the S phase rate, cells are either better able to repair or better able to replicate damaged DNA. In this study, we determine the effects of mutations that impair S phase regulation on the ability of excision repair-defective cells to replicate irreparably UV-damaged DNA. We assay survival after UV irradiation, as well as the genetic consequences of replicating a damaged template, namely mutation and sister chromatid exchange induction. We find that RAD9, RAD17, RAD24, and MEC3 are required for UV-induced (although not spontaneous) mutagenesis, and that RAD9 and RAD17 (but not REV3, RAD24, and MEC3) are required for maximal induction of replication-dependent sister chromatid exchange. Therefore, checkpoint genes not only control cell cycle progression in response to damage, but also play a role in accommodating DNA damage during replication. PMID:9725831</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/9725831','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/9725831"><span>The Saccharomyces cerevisiae RAD9, RAD17, RAD24 and MEC3 genes are required for tolerating irreparable, ultraviolet-induced DNA damage.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Paulovich, A G; Armour, C D; Hartwell, L H</p>
<p>1998-09-01</p>
<p>In wild-type Saccharomyces cerevisiae, a checkpoint slows the rate of progression of an ongoing S phase in response to exposure to a DNA-alkylating agent. Mutations that eliminate S phase regulation also confer sensitivity to alkylating agents, leading us to suggest that, by regulating the S phase rate, cells are either better able to repair or better able to replicate damaged DNA. In this study, we determine the effects of mutations that impair S phase regulation on the ability of excision repair-defective cells to replicate irreparably UV-damaged DNA. We assay survival after UV irradiation, as well as the genetic consequences of replicating a damaged template, namely mutation and sister chromatid exchange induction. We find that RAD9, RAD17, RAD24, and MEC3 are required for UV-induced (although not spontaneous) mutagenesis, and that RAD9 and RAD17 (but not REV3, RAD24, and MEC3) are required for maximal induction of replication-dependent sister chromatid exchange. Therefore, checkpoint genes not only control cell cycle progression in response to damage, but also play a role in accommodating DNA damage during replication.</p>
</li>
</ol>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/133767-unique-double-de-novo-structural-rearrangements-chromosome-xx-del-q13q23-xx-inv-dup-q13q23-infant-minor-congenital-abnormalities-delayed-development','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/133767-unique-double-de-novo-structural-rearrangements-chromosome-xx-del-q13q23-xx-inv-dup-q13q23-infant-minor-congenital-abnormalities-delayed-development"><span>Unique double de novo structural rearrangements for chromosome 11 with 46,XX,del(11)(q13q23)/46,XX,inv dup(11)(q13q23) in an infant with minor congenital abnormalities and delayed development</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Tharapel, A.T.; Zhao, J.; Smith, M.E.</p>
<p>1994-09-01</p>
<p>Reported here is a patient with two most unusual structural rearrangements, both involving chromosome 11. The first cell line showed an interstitial deletion of a chromosome 11 with a 46,XX,del(11)(q13q23) chromosome complement. In the second cell line, one of the chromosome 11s had a duplication for the exact region, (11)(q13q23), that was deleted in the first cell line. This duplication also appeared to be inverted with karyotype 46,XX,inv dup(11)(q13q23). Interestingly, chromosome analysis did not reveal a normal cell line and the two abnormal cell lines were present in a 1:1 ratio. Parental chromosome analyses showed normal karyotypes. The patient wasmore » referred for genetic evaluation because of developmental delay. Minor congenital anomalies presented on physical examination included: weight and height at or below the 5th percentile, microcephaly, downward slanting palpebral fissures, severe clinodactyly of one toe, bilateral short fifth fingers and a broad based gait. Results of the MRI and urine metabolic screen were normal. Two hypotheses are advanced to explain the origin of the abnormality. It is most likely that the abnormality arose as a postzygotic event at the very early zygotic division. During the first DNA synthesis after fertilization and before the zygotic division, DNA synthesis errors could result in two chromatids, one with a deletion and the other with a duplication. It is also possible that after the DNA synthesis prior to the first cell division, the chromatids of the same chromosome 11 for unknown reasons were involved in uneven double somatic crossing over events resulting in deleted and duplicated chromatids, respectively. The 1:1 cell ratio found in the patient and the apparent non-existence of a normal cell line further suggest that the origin of the abnormality was post-zygotic.« less</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/437790','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/437790"><span>Chromosome mutations and chromosome stability in children treated with different regimes of immunosuppressive drugs.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Schuler, D; Dobos, M; Fekete, G; Miltényi, M; Kalmár, L</p>
<p>1979-01-01</p>
<p>The chromosome mutations and the number of sister chromatid exchanges induced by different kinds of immunosuppressive treatment were investigated in children and adults with certain types of renal diseases. The aim of the study was to find among the treatment schedules those promising good therapeutic results with the least mutagenic effects. A slightly decreased chromosome stability was found in the patients treated by cyclophosphamide therapy.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/5120376-induction-sister-chromatid-exchange-preimplantation-mouse-embryos-vitro-sup-thymidine-ultraviolet-light-combination-caffeine','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/5120376-induction-sister-chromatid-exchange-preimplantation-mouse-embryos-vitro-sup-thymidine-ultraviolet-light-combination-caffeine"><span>Induction of sister chromatid exchange in preimplantation mouse embryos in vitro by /sup 3/H-thymidine or ultraviolet light in combination with caffeine</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Mueller, W.U.S.; Spindle, A.</p>
<p>1986-01-01</p>
<p>Preimplantation mouse embryos were exposed in vitro to /sup 3/H-thymidine (25, 100, or 250 Bq/ml) or ultraviolet (UV) light (1.35 or 4.05 J/m2), either alone or in combination with caffeine (1 mM with /sup 3/H-thymidine and 0.5 mM with UV light). Exposure to /sup 3/H-thymidine lasted for 2 days, from the two-cell stage to the late morula/early blastocyst stage, and UV radiation was applied acutely at the late morula/early blastocyst stage. The effects were quantified by the sister chromatid exchange (SCE) assay. All three agents induced SCEs when used singly. /sup 3/H-thymidine was effective in inducing SCEs only at 250more » Bq/ml, whereas UV light was effective at both fluences. Although caffeine did not induce SCEs when it was added before exposure to bromodeoxyuridine (BrdUrd), which is used to visualize SCEs, it did induce SCEs when present during the entire culture period (/sup 3/H-thymidine experiments) or during incubation in BrdUrd (UV experiments). Caffeine markedly enhanced the SCE-inducing effect of UV light but did not influence the effect of /sup 3/H-thymidine.« less</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2013AdSpR..51..450H','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2013AdSpR..51..450H"><span>No significant level of inheritable interchromosomal aberrations in the progeny of bystander primary human fibroblasts after alpha particle irradiation</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p>
<p>Hu, Burong; Zhu, Jiayun; Zhou, Hongning; Hei, Tom K.</p>
<p>2013-02-01</p>
<p>A major concern for bystander effects is the probability that normal healthy cells adjacent to the irradiated cells become genomically unstable and undergo further carcinogenesis after therapeutic irradiation or space mission where astronauts are exposed to low dose of heavy ions. Genomic instability is a hallmark of cancer cells. In the present study, two irradiation protocols were performed in order to ensure pure populations of bystander cells and the genomic instability in their progeny were investigated. After irradiation, chromosomal aberrations of cells were analyzed at designated time points using G2 phase premature chromosome condensation (G2-PCC) coupled with Giemsa staining and with multiplex fluorescent in situ hybridization (mFISH). Our Giemsa staining assay demonstrated that elevated yields of chromatid breaks were induced in the progeny of pure bystander primary fibroblasts up to 20 days after irradiation. mFISH assay showed no significant level of inheritable interchromosomal aberrations were induced in the progeny of the bystander cell groups, while the fractions of gross aberrations (chromatid breaks or chromosomal breaks) significantly increased in some bystander cell groups. These results suggest that genomic instability occurred in the progeny of the irradiation associated bystander normal fibroblasts exclude the inheritable interchromosomal aberration.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4712966','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4712966"><span>Chromosomal Integrity after UV Irradiation Requires FANCD2-Mediated Repair of Double Strand Breaks</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Federico, María Belén; Vallerga, María Belén; Radl, Analía; Paviolo, Natalia Soledad; Bocco, José Luis; Di Giorgio, Marina; Soria, Gastón; Gottifredi, Vanesa</p>
<p>2016-01-01</p>
<p>Fanconi Anemia (FA) is a rare autosomal recessive disorder characterized by hypersensitivity to inter-strand crosslinks (ICLs). FANCD2, a central factor of the FA pathway, is essential for the repair of double strand breaks (DSBs) generated during fork collapse at ICLs. While lesions different from ICLs can also trigger fork collapse, the contribution of FANCD2 to the resolution of replication-coupled DSBs generated independently from ICLs is unknown. Intriguingly, FANCD2 is readily activated after UV irradiation, a DNA-damaging agent that generates predominantly intra-strand crosslinks but not ICLs. Hence, UV irradiation is an ideal tool to explore the contribution of FANCD2 to the DNA damage response triggered by DNA lesions other than ICL repair. Here we show that, in contrast to ICL-causing agents, UV radiation compromises cell survival independently from FANCD2. In agreement, FANCD2 depletion does not increase the amount of DSBs generated during the replication of UV-damaged DNA and is dispensable for UV-induced checkpoint activation. Remarkably however, FANCD2 protects UV-dependent, replication-coupled DSBs from aberrant processing by non-homologous end joining, preventing the accumulation of micronuclei and chromatid aberrations including non-homologous chromatid exchanges. Hence, while dispensable for cell survival, FANCD2 selectively safeguards chromosomal stability after UV-triggered replication stress. PMID:26765540</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/5738888-enhanced-response-induction-sister-chromatid-exchange-gamma-radiation-neurofibromatosis','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/5738888-enhanced-response-induction-sister-chromatid-exchange-gamma-radiation-neurofibromatosis"><span>Enhanced response to the induction of sister chromatid exchange by gamma radiation in neurofibromatosis</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Hafez, M.; Abd el-Nabi, S.M.; el-Wehedi, G.</p>
<p></p>
<p>The study included 8 unrelated patients with neurofibromatosis, and 10 unrelated normal and healthy persons as controls. Whole blood samples were divided into plastic T flasks and exposed at room temperature to gamma rays. The radiation dose was 36 rad/minute, and the doses delivered were 0, 75, 150 and 300 rad. The lymphocytes were cultured in (RPMI) 1640 tissue culture medium and autologous serum (20%). Phytohemagglutinin and bromodeoxyuridine (Brdu) (10 microM) were added at initiation of culture and harvesting was done 64 to 68 hours after culture initiation. Slides were coded, differential staining was done, and sister chromatid exchanges (SCEs)more » and aberrations (gaps, breaks, dicentrics, fragments and minutes) were counted. In the controls no significant increase in frequency of SCE has been found (P greater than 0.5). In the patients, the frequencies significantly increased with the increase of dose of irradiation (P less than 0.001). Furthermore, after irradiation, the incidence of gaps, breaks, and dicentrics were significantly increased in patients compared with controls. Moreover, the incidence increased with the increase in the dose of radiation. The results are discussed with a conclusion that the results add to the indication of a genetic predisposition to develop cancer in neurofibromatosis patients.« less</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1931544','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1931544"><span>Meiotic Parthenogenesis in a Root-Knot Nematode Results in Rapid Genomic Homozygosity</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Liu, Qingli L.; Thomas, Varghese P.; Williamson, Valerie M.</p>
<p>2007-01-01</p>
<p>Many isolates of the plant-parasitic nematode Meloidogyne hapla reproduce by facultative meiotic parthenogenesis. Sexual crosses can occur, but, in the absence of males, the diploid state appears to be restored by reuniting sister chromosomes of a single meiosis. We have crossed inbred strains of M. hapla that differ in DNA markers and produced hybrids and F2 lines. Here we show that heterozygous M. hapla females, upon parthenogenetic reproduction, produce progeny that segregate 1:1 for the presence or absence of dominant DNA markers, as would be expected if sister chromosomes are rejoined, rather than the 3:1 ratio typical of a Mendelian cross. Codominant markers also segregate 1:1 and heterozygotes are present at low frequency (<3%). Segregation patterns and recombinant analysis indicate that a homozygous condition is prevalent for markers flanking recombination events, suggesting that recombination occurs preferentially as four-strand exchanges at similar locations between both pairs of non-sister chromatids. With this mechanism, meiotic parthenogenesis would be expected to result in rapid genomic homozygosity. This type of high negative crossover interference coupled with positive chromatid interference has not been observed in fungal or other animal systems in which it is possible to examine the sister products of a single meiosis and may indicate that meiotic recombination in this nematode has novel features. PMID:17483427</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24077888','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24077888"><span>Identification and diversity of functional centromere satellites in the wild rice species Oryza brachyantha.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Yi, Chuandeng; Zhang, Wenli; Dai, Xibin; Li, Xing; Gong, Zhiyun; Zhou, Yong; Liang, Guohua; Gu, Minghong</p>
<p>2013-12-01</p>
<p>The centromere is a key chromosomal component for sister chromatid cohesion and is the site for kinetochore assembly and spindle fiber attachment, allowing each sister chromatid to faithfully segregate to each daughter cell during cell division. It is not clear what types of sequences act as functional centromeres and how centromere sequences are organized in Oryza brachyantha, an FF genome species. In this study, we found that the three classes of centromere-specific CentO-F satellites (CentO-F1, CentO-F2, and CentOF3) in O. brachyantha share no homology with the CentO satellites in Oryza sativa. The three classes of CentO-F satellites are all located within the chromosomal regions to which the spindle fibers attach and are characterized by megabase tandem arrays that are flanked by centromere-specific retrotransposons, CRR-F, in the O. brachyantha centromeres. Although these CentO-F satellites are quantitatively variable among 12 O. brachyantha centromeres, immunostaining with an antibody specific to CENH3 indicates that they are colocated with CENH3 in functional centromere regions. Our results demonstrate that the three classes of CentO-F satellites may be the major components of functional centromeres in O. brachyantha.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26765540','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26765540"><span>Chromosomal Integrity after UV Irradiation Requires FANCD2-Mediated Repair of Double Strand Breaks.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Federico, María Belén; Vallerga, María Belén; Radl, Analía; Paviolo, Natalia Soledad; Bocco, José Luis; Di Giorgio, Marina; Soria, Gastón; Gottifredi, Vanesa</p>
<p>2016-01-01</p>
<p>Fanconi Anemia (FA) is a rare autosomal recessive disorder characterized by hypersensitivity to inter-strand crosslinks (ICLs). FANCD2, a central factor of the FA pathway, is essential for the repair of double strand breaks (DSBs) generated during fork collapse at ICLs. While lesions different from ICLs can also trigger fork collapse, the contribution of FANCD2 to the resolution of replication-coupled DSBs generated independently from ICLs is unknown. Intriguingly, FANCD2 is readily activated after UV irradiation, a DNA-damaging agent that generates predominantly intra-strand crosslinks but not ICLs. Hence, UV irradiation is an ideal tool to explore the contribution of FANCD2 to the DNA damage response triggered by DNA lesions other than ICL repair. Here we show that, in contrast to ICL-causing agents, UV radiation compromises cell survival independently from FANCD2. In agreement, FANCD2 depletion does not increase the amount of DSBs generated during the replication of UV-damaged DNA and is dispensable for UV-induced checkpoint activation. Remarkably however, FANCD2 protects UV-dependent, replication-coupled DSBs from aberrant processing by non-homologous end joining, preventing the accumulation of micronuclei and chromatid aberrations including non-homologous chromatid exchanges. Hence, while dispensable for cell survival, FANCD2 selectively safeguards chromosomal stability after UV-triggered replication stress.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/7300853','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/7300853"><span>Sister-chromatid exchanges in lymphocytes in women with cancer of the breast.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Husum, B; Wulf, H C; Niebuhr, E</p>
<p>1981-10-01</p>
<p>Examination of sister-chromatid exchanges (SCE) in lymphocytes may be useful for the evaluation of exposure to mutagens/carcinogens. Information of a possible association between SCE and cancer is scarce. We therefore examined SCE in peripheral lymphocytes in 131 women, aged 17-90 years (median 51.8 years), coming to operation because of a tumor of the breast. Venous blood samples were cultivated during PHA stimulation in the presence of BrdU. After treatment with colcemid (R), fixation, treatment with bisbenzimide and staining with Giemsa, 30 metaphases were scored in each specimen. 52 patients with peroperatively demonstrated carcinoma of the breast had 9.39 +/- 0.17 SCE/cell and the remaining 79 women with non-malignant fibroadenomatosis had 9.88 +/- 0.18 SCE/cell. By multiple regression analysis it appeared that the character of the tumor, the patient's age, hormone treatment and preoperative examination by mammography all were without significant influence on the SCE rate. A statistically significant correlation was found between SCE and cigarette smoking. THe 45 cigarette-smoking patients had 10.49 +/- 0.23 SCE/cell compared with 9.26 +/- 0.13 SCE/cell in the 86 non-smokers. It was concluded that spontaneous SCE in lymphocytes is not an indicator of carcinoma of the breast.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4790872','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4790872"><span>The Opposing Actions of Arabidopsis CHROMOSOME TRANSMISSION FIDELITY7 and WINGS APART-LIKE1 and 2 Differ in Mitotic and Meiotic Cells</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Mitra, Sayantan; Yang, Xiaohui</p>
<p>2016-01-01</p>
<p>Sister chromatid cohesion, which is mediated by the cohesin complex, is essential for the proper segregation of chromosomes during mitosis and meiosis. Stable binding of cohesin with chromosomes is regulated in part by the opposing actions of CTF7 (CHROMOSOME TRANSMISSION FIDELITY7) and WAPL (WINGS APART-LIKE). In this study, we characterized the interaction between Arabidopsis thaliana CTF7 and WAPL by conducting a detailed analysis of wapl1-1 wapl2 ctf7 plants. ctf7 plants exhibit major defects in vegetative growth and development and are completely sterile. Inactivation of WAPL restores normal growth, mitosis, and some fertility to ctf7 plants. This shows that the CTF7/WAPL cohesin system is not essential for mitosis in vegetative cells and suggests that plants may contain a second mechanism to regulate mitotic cohesin. WAPL inactivation restores cohesin binding and suppresses ctf7-associated meiotic cohesion defects, demonstrating that WAPL and CTF7 function as antagonists to regulate meiotic sister chromatid cohesion. The ctf7 mutation only had a minor effect on wapl-associated defects in chromosome condensation and centromere association. These results demonstrate that WAPL has additional roles that are independent of its role in regulating chromatin-bound cohesin. PMID:26813623</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3442196','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3442196"><span>Perturbation of Incenp function impedes anaphase chromatid movements and chromosomal passenger protein flux at centromeres</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Ahonen, Leena J.; Kukkonen, Anu M.; Pouwels, Jeroen; Bolton, Margaret A.; Jingle, Christopher D.; Stukenberg, P. Todd; Kallio, Marko J.</p>
<p>2012-01-01</p>
<p>Incenp is an essential mitotic protein that, together with Aurora B, Survivin, and Borealin, forms the core of the chromosomal passenger protein complex (CPC). The CPC regulates various mitotic processes and functions to maintain genomic stability. The proper subcellular localization of the CPC and its full catalytic activity require the presence of each core subunit in the complex. We have investigated the mitotic tasks of the CPC using a function blocking antibody against Incenp microinjected into cells at different mitotic phases. This method allowed temporal analysis of CPC functions without perturbation of complex assembly or activity prior to injection. We have also studied the dynamic properties of Incenp and Aurora B using fusion protein photobleaching. We found that in early mitotic cells, Incenp and Aurora B exhibit dynamic turnover at centromeres, which is prevented by the anti-Incenp antibody. In these cells, the loss of centromeric CPC turnover is accompanied by forced mitotic exit without the execution of cytokinesis. Introduction of anti-Incenp antibody into early anaphase cells causes abnormalities in sister chromatid separation through defects in anaphase spindle functions. In summary, our data uncovers new mitotic roles for the CPC in anaphase and proposes that CPC turnover at centromeres modulates spindle assembly checkpoint signaling. PMID:18784935</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/18784935','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/18784935"><span>Perturbation of Incenp function impedes anaphase chromatid movements and chromosomal passenger protein flux at centromeres.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Ahonen, Leena J; Kukkonen, Anu M; Pouwels, Jeroen; Bolton, Margaret A; Jingle, Christopher D; Stukenberg, P Todd; Kallio, Marko J</p>
<p>2009-02-01</p>
<p>Incenp is an essential mitotic protein that, together with Aurora B, Survivin, and Borealin, forms the core of the chromosomal passenger protein complex (CPC). The CPC regulates various mitotic processes and functions to maintain genomic stability. The proper subcellular localization of the CPC and its full catalytic activity require the presence of each core subunit in the complex. We have investigated the mitotic tasks of the CPC using a function blocking antibody against Incenp microinjected into cells at different mitotic phases. This method allowed temporal analysis of CPC functions without perturbation of complex assembly or activity prior to injection. We have also studied the dynamic properties of Incenp and Aurora B using fusion protein photobleaching. We found that in early mitotic cells, Incenp and Aurora B exhibit dynamic turnover at centromeres, which is prevented by the anti-Incenp antibody. In these cells, the loss of centromeric CPC turnover is accompanied by forced mitotic exit without the execution of cytokinesis. Introduction of anti-Incenp antibody into early anaphase cells causes abnormalities in sister chromatid separation through defects in anaphase spindle functions. In summary, our data uncovers new mitotic roles for the CPC in anaphase and proposes that CPC turnover at centromeres modulates spindle assembly checkpoint signaling.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/2687630','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/2687630"><span>Induction of sister chromatid exchanges and cell division delays in human lymphocytes by the anti-tumour agent homo-aza-steroidal ester of p-bis(2-chloroethyl)aminophenoxy acetic acid.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Tselepi, M R; Demopoulos, N A; Catsoulacos, P</p>
<p>1989-09-01</p>
<p>3 beta-Hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam-p-bis(2-chloroethyl) aminophenoxyacetate (NSC 294859) is a new modified steroidal alkylating agent. This compound was given by i.p. administration to mice bearing different types of tumour. It was found to exhibit good activity in L1210 and P388 leukaemias with maintenance of activity against advanced tumours. The treatment of colon 26 tumour and B16 melanoma resulted in positive antineoplastic activity. The drug was not shown to be active in a melphalan-resistant P388 line. In this study, NSC 294859 was found to be effective in causing statistically significant increases in sister-chromatid exchange (SCE) rates and cell division delays. The alkylating agent component, p-bis-(2-chloroethyl)aminophenoxy acetic acid, was shown to be less effective than the parent compound, while the modified steroid component, 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam, showed no effect. There were no statistically significant differences among donors regarding the induction of SCEs and replication indices (RIs) for the compounds tested.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23503090','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23503090"><span>No significant level of inheritable interchromosomal aberrations in the progeny of bystander primary human fibroblast after alpha particle irradiation.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Hu, Burong; Zhu, Jiayun; Zhou, Hongning; Hei, Tom K</p>
<p>2013-02-01</p>
<p>A major concern for bystander effects is the probability that normal healthy cells adjacent to the irradiated cells become genomically unstable and undergo further carcinogenesis after therapeutic irradiation or space mission where astronauts are exposed to low dose of heavy ions. Genomic instability is a hallmark of cancer cells. In the present study, two irradiation protocols were performed in order to ensure pure populations of bystander cells and the genomic instability in their progeny were investigated. After irradiation, chromosomal aberrations of cells were analyzed at designated time points using G 2 phase premature chromosome condensation (G 2 -PCC) coupled with Giemsa staining and with multiplex fluorescent in situ hybridization (mFISH). Our Giemsa staining assay demonstrated that elevated yields of chromatid breaks were induced in the progeny of pure bystander primary fibroblasts up to 20 days after irradiation. MFISH assay showed no significant level of inheritable interchromosomal aberrations were induced in the progeny of the bystander cell groups, while the fractions of gross aberrations (chromatid breaks or chromosomal breaks) significantly increased in some bystander cell groups. These results suggest that genomic instability occurred in the progeny of the irradiation associated bystander normal fibroblasts exclude the inheritable interchromosomal aberration.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/7116324','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/7116324"><span>Chromosome-damaging activity of saliva of betel nut and tobacco chewers.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Stich, H F; Stich, W</p>
<p>1982-01-01</p>
<p>Saliva of volunteers chewing betel quid, cured betel nut (Areca catechu), betel leaves (Piper betle), a mixture of quid ingredients (dried betel nut flakes, catechu, cardamon, lime, copra and menthol) and Indian tobacco was collected and examined for its genotoxic activity. Chromosome aberrations (chromatid breaks and chromatid exchanges) in Chinese hamster ovary (CHO) cells were used to estimate the genotoxic effect. No detectable levels of clastogenic activity were observed in the saliva of non-chewing individuals. After 5 min of chewing betel quid, betel nut, betel leaves, quid ingredients and Indian tobacco, the saliva samples showed relatively potent clastogenic activities. The addition of transition metals Mn2+ and Cu2+ to the saliva samples of betel nut and Indian tobacco chewers enhanced their clastogenic activities, whereas Fe3+ increased the clastogenicity of the betel nut saliva but decreased the genotoxic effect of the saliva of Indian tobacco chewers. After removal of the betel quid or its components from the mouth, the clastogenic activity disappeared within 5 min. The western-type chewing tobacco did not produce a genotoxic activity in the saliva of chewers. A possible association between the genotoxicity in the saliva of betel quid chewers and the development of oral, pharyngeal and esophageal carcinomas is discussed.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3439829','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3439829"><span>Diverse Developmental Disorders from The One Ring: Distinct Molecular Pathways Underlie the Cohesinopathies</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Horsfield, Julia A.; Print, Cristin G.; Mönnich, Maren</p>
<p>2012-01-01</p>
<p>The multi-subunit protein complex, cohesin, is responsible for sister chromatid cohesion during cell division. The interaction of cohesin with DNA is controlled by a number of additional regulatory proteins. Mutations in cohesin, or its regulators, cause a spectrum of human developmental syndromes known as the “cohesinopathies.” Cohesinopathy disorders include Cornelia de Lange Syndrome and Roberts Syndrome. The discovery of novel roles for chromatid cohesion proteins in regulating gene expression led to the idea that cohesinopathies are caused by dysregulation of multiple genes downstream of mutations in cohesion proteins. Consistent with this idea, Drosophila, mouse, and zebrafish cohesinopathy models all show altered expression of developmental genes. However, there appears to be incomplete overlap among dysregulated genes downstream of mutations in different components of the cohesion apparatus. This is surprising because mutations in all cohesion proteins would be predicted to affect cohesin’s roles in cell division and gene expression in similar ways. Here we review the differences and similarities between genetic pathways downstream of components of the cohesion apparatus, and discuss how such differences might arise, and contribute to the spectrum of cohesinopathy disorders. We propose that mutations in different elements of the cohesion apparatus have distinct developmental outcomes that can be explained by sometimes subtly different molecular effects. PMID:22988450</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=20040142117&hterms=kaplan&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D50%26Ntt%3Dkaplan','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=20040142117&hterms=kaplan&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D50%26Ntt%3Dkaplan"><span>The evolution of chromosomal instability in Chinese hamster cells: a changing picture?</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p>
<p>Ponnaiya, B.; Limoli, C. L.; Corcoran, J.; Kaplan, M. I.; Hartmann, A.; Morgan, W. F.</p>
<p>1998-01-01</p>
<p>PURPOSE: To investigate the kinetics of chromosomal instability induced in clones of Chinese hamster cells following X-irradiation. MATERIALS AND METHODS: X-irradiated clones of GM10115, human-hamster hybrid cells containing a single human chromosome 4 (HC4), have been previously established. These clones were defined as unstable if they contained > or = three subpopulations of cells with unique rearrangements of HC4 as detected by FISH. Stable and unstable clones were analysed by FISH and Giemsa staining at various times post-irradiation. RESULTS: While most of the stable clones continued to show chromosomal stability of HC4 over time, one became marginally unstable at approximately 45 population doublings post-irradiation. Clones exhibiting chromosomal instability had one of several fates. Many of the unstable clones were showed similar levels of instability over time. However, one unstable clone became stable with time in culture, while another became even more unstable over time. Cytogenetic analyses of all clones after Giemsa staining indicated that in some clones the hamster chromosomes were rearranged independent of HC4, demonstrating increased frequencies of chromatid breaks and dicentric chromosomes. The majority of the unstable clones also had higher yields of chromatid gaps. CONCLUSIONS: These data demonstrate the dynamic nature of chromosomal instability as measured by two different cytogenetic assays.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5587752','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5587752"><span>FANCJ helicase controls the balance between short- and long-tract gene conversions between sister chromatids</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Nath, Sarmi; Somyajit, Kumar; Mishra, Anup; Scully, Ralph</p>
<p>2017-01-01</p>
<p>Abstract The FANCJ DNA helicase is linked to hereditary breast and ovarian cancers as well as bone marrow failure disorder Fanconi anemia (FA). Although FANCJ has been implicated in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR), the molecular mechanism underlying the tumor suppressor functions of FANCJ remains obscure. Here, we demonstrate that FANCJ deficient human and hamster cells exhibit reduction in the overall gene conversions in response to a site-specific chromosomal DSB induced by I-SceI endonuclease. Strikingly, the gene conversion events were biased in favour of long-tract gene conversions in FANCJ depleted cells. The fine regulation of short- (STGC) and long-tract gene conversions (LTGC) by FANCJ was dependent on its interaction with BRCA1 tumor suppressor. Notably, helicase activity of FANCJ was essential for controlling the overall HR and in terminating the extended repair synthesis during sister chromatid recombination (SCR). Moreover, cells expressing FANCJ pathological mutants exhibited defective SCR with an increased frequency of LTGC. These data unravel the novel function of FANCJ helicase in regulating SCR and SCR associated gene amplification/duplications and imply that these functions of FANCJ are crucial for the genome maintenance and tumor suppression. PMID:28911102</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25172298','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25172298"><span>Evaluation of cytogenetic and DNA damage in human lymphocytes treated with adrenaline in vitro.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Djelić, Ninoslav; Radaković, Milena; Spremo-Potparević, Biljana; Zivković, Lada; Bajić, Vladan; Stevanović, Jevrosima; Stanimirović, Zoran</p>
<p>2015-02-01</p>
<p>Catechol groups can be involved in redox cycling accompanied by generation of reactive oxygen species (ROS) which may lead to oxidative damage of cellular macromolecules including DNA. The objective of this investigation was to evaluate possible genotoxic effects of a natural catecholamine adrenaline in cultured human lymphocytes using cytogenetic (sister chromatid exchange and micronuclei) and the single cell gel electrophoresis (Comet) assay. In cytogenetic tests, six experimental concentrations of adrenaline were used in a range from 0.01-500 μM. There were no indications of genotoxic effects of adrenaline in sister chromatid exchange and micronucleus tests. However, at four highest concentrations of adrenaline (5 μM, 50 μM, 150 μM and 300 μM) we observed a decreased mitotic index and cell-cycle delay. In addition, in the Comet assay we used adrenaline in a range from 0.0005-500 μM, at two treatment times: 15 min or 60 min. In contrast to cytogenetic analysis, there was a dose-dependent increase of DNA damage detected in the Comet assay. These effects were significantly reduced by concomitant treatment with quercetin or catalase. Therefore, the obtained results indicate that adrenaline may exhibit genotoxic effects in cultured human lymphocytes, most likely due to production of reactive oxygen species. Copyright © 2014 Elsevier Ltd. All rights reserved.</p>
</li>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3826130','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3826130"><span>Microcystin-LR and Cylindrospermopsin Induced Alterations in Chromatin Organization of Plant Cells</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Máthé, Csaba; M-Hamvas, Márta; Vasas, Gábor</p>
<p>2013-01-01</p>
<p>Cyanobacteria produce metabolites with diverse bioactivities, structures and pharmacological properties. The effects of microcystins (MCYs), a family of peptide type protein-phosphatase inhibitors and cylindrospermopsin (CYN), an alkaloid type of protein synthesis blocker will be discussed in this review. We are focusing mainly on cyanotoxin-induced changes of chromatin organization and their possible cellular mechanisms. The particularities of plant cells explain the importance of such studies. Preprophase bands (PPBs) are premitotic cytoskeletal structures important in the determination of plant cell division plane. Phragmoplasts are cytoskeletal structures involved in plant cytokinesis. Both cyanotoxins induce the formation of multipolar spindles and disrupted phragmoplasts, leading to abnormal sister chromatid segregation during mitosis. Thus, MCY and CYN are probably inducing alterations of chromosome number. MCY induces programmed cell death: chromatin condensation, nucleus fragmentation, necrosis, alterations of nuclease and protease enzyme activities and patterns. The above effects may be related to elevated reactive oxygen species (ROS) and/or disfunctioning of microtubule associated proteins. Specific effects: MCY-LR induces histone H3 hyperphosphorylation leading to incomplete chromatid segregation and the formation of micronuclei. CYN induces the formation of split or double PPB directly related to protein synthesis inhibition. Cyanotoxins are powerful tools in the study of plant cell organization. PMID:24084787</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11287309','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11287309"><span>Genotoxic effects of styrene-7,8-oxide in human white blood cells: comet assay in relation to the induction of sister-chromatid exchanges and micronuclei.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Laffon, B; Pásaro, E; Méndez, J</p>
<p>2001-04-05</p>
<p>Styrene is used in the production of plastics, resins and rubber. The highest human exposures to styrene take place by inhalation during the production of fiberglass reinforced plastics. Styrene is metabolized mainly in the liver to styrene-7,8-oxide (SO), its principal in vivo mutagenic metabolite. In this study, human peripheral white blood cells were exposed to several SO concentrations (10-200 microM) in order to evaluate its genotoxic properties by means of comet assay, sister-chromatid exchanges (SCE) and cytokinesis-blocked micronucleus (MN) test, in addition to determine its clastogenic or aneugenic properties by combining MN with fluorescence in situ hybridization (FISH) procedures. Our results show that SO induces DNA damage, SCE and MN in human leukocytes in vitro at concentrations above 50 microM, and that there is a strong relationship between DNA damage, as measured by the comet assay, and cytogenetic damage induced by SO at the doses employed. SO shows preferentially a clastogenic activity and produces a cytostatic effect at high doses, reflected by the significant decrease of the calculated proliferation indices. A good dose-effect relationship is obtained in the three tests performed at the concentration range assayed.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/134375-interstitial-telomeric-sequences-human-chromosomes-cluster-common-fragile-sites-mutagen-sensitive-sites-viral-integration-sites-cancer-breakpoints-proto-oncogenes-breakpoints-involved-primate-evolution','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/134375-interstitial-telomeric-sequences-human-chromosomes-cluster-common-fragile-sites-mutagen-sensitive-sites-viral-integration-sites-cancer-breakpoints-proto-oncogenes-breakpoints-involved-primate-evolution"><span>Interstitial telomeric sequences in human chromosomes cluster with common fragile sites, mutagen sensitive sites, viral integration sites, cancer breakpoints, proto-oncogenes and breakpoints involved in primate evolution</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Adekunle, S.S.A.; Wyandt, H.; Mark, H.F.L.</p>
<p>1994-09-01</p>
<p>Recently we mapped the telomeric repeat sequences to 111 interstitial sites in the human genome and to sites of gaps and breaks induced by aphidicolin and sister chromatid exchange sites detected by BrdU. Many of these sites correspond to conserved fragile sites in man, gorilla and chimpazee, to sites of conserved sister chromatid exchange in the mammalian X chromosome, to mutagenic sensitive sites, mapped locations of proto-oncogenes, breakpoints implicated in primate evolution and to breakpoints indicated as the sole anomaly in neoplasia. This observation prompted us to investigate if the interstitial telomeric sites cluster with these sites. An extensive literaturemore » search was carried out to find all the available published sites mentioned above. For comparison, we also carried out a statistical analysis of the clustering of the sites of the telomeric repeats with the gene locations where only nucleotide mutations have been observed as the only chromosomal abnormality. Our results indicate that the telomeric repeats cluster most with fragile sites, mutagenic sensitive sites and breakpoints implicated in primate evolution and least with cancer breakpoints, mapped locations of proto-oncogenes and other genes with nucleotide mutations.« less</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('http://www.dtic.mil/docs/citations/ADB258879','DTIC-ST'); return false;" href="http://www.dtic.mil/docs/citations/ADB258879"><span>Chromatid Paints: A New Method for Detecting Tumor-Specific Chromosomal Inversions</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.dtic.mil/">DTIC Science & Technology</a></p>
<p></p>
<p>1999-10-01</p>
<p>chromosomal DNA as a template for DNA polymerization. The cloning procedure requires copying DNA from fixed cells attached to a glass substrate. Any...achieved by initially fixing cells in methanol and adding acetic acid just before dropping cells onto coverslips. The procedure itself is a novel and...human hybrid cells containing one human #11 chromosome were fixed and dropped onto microscope coverslips. These cells had been synchronized by mitotic</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29043643','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29043643"><span>Imaging of DNA Ultrafine Bridges in Budding Yeast.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Quevedo, Oliver; Lisby, Michael</p>
<p>2018-01-01</p>
<p>DNA ultrafine bridges (UFBs) are a type of chromatin-free DNA bridges that connect sister chromatids in anaphase and pose a threat to genome stability. However, little is known about the origin of these structures, and how they are sensed and resolved by the cell. In this chapter, we review tools and methods for studying UFBs by fluorescence microscopy including chemical and genetic approaches to induce UFBs in the model organism Saccharomyces cerevisiae.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3003188','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3003188"><span>Sister acts: coordinating DNA replication and cohesion establishment</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Sherwood, Rebecca; Takahashi, Tatsuro S.; Jallepalli, Prasad V.</p>
<p>2010-01-01</p>
<p>The ring-shaped cohesin complex links sister chromatids and plays crucial roles in homologous recombination and mitotic chromosome segregation. In cycling cells, cohesin's ability to generate cohesive linkages is restricted to S phase and depends on loading and establishment factors that are intimately connected to DNA replication. Here we review how cohesin is regulated by the replication machinery, as well as recent evidence that cohesin itself influences how chromosomes are replicated. PMID:21159813</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3979685','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3979685"><span>Differential Radiosensitivity Phenotypes of DNA-PKcs Mutations Affecting NHEJ and HRR Systems following Irradiation with Gamma-Rays or Very Low Fluences of Alpha Particles</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Little, John B.; Kato, Takamitsu A.; Shih, Hung-Ying; Xie, Xian-Jin; Wilson Jr., Paul F.; Brogan, John R.; Kurimasa, Akihiro; Chen, David J.; Bedford, Joel S.; Chen, Benjamin P. C.</p>
<p>2014-01-01</p>
<p>We have examined cell-cycle dependence of chromosomal aberration induction and cell killing after high or low dose-rate γ irradiation in cells bearing DNA-PKcs mutations in the S2056 cluster, the T2609 cluster, or the kinase domain. We also compared sister chromatid exchanges (SCE) production by very low fluences of α-particles in DNA-PKcs mutant cells, and in homologous recombination repair (HRR) mutant cells including Rad51C, Rad51D, and Fancg/xrcc9. Generally, chromosomal aberrations and cell killing by γ-rays were similarly affected by mutations in DNA-PKcs, and these mutant cells were more sensitive in G1 than in S/G2 phase. In G1-irradiated DNA-PKcs mutant cells, both chromosome- and chromatid-type breaks and exchanges were in excess than wild-type cells. For cells irradiated in late S/G2 phase, mutant cells showed very high yields of chromatid breaks compared to wild-type cells. Few exchanges were seen in DNA-PKcs-null, Ku80-null, or DNA-PKcs kinase dead mutants, but exchanges in excess were detected in the S2506 or T2609 cluster mutants. SCE induction by very low doses of α-particles is resulted from bystander effects in cells not traversed by α-particles. SCE seen in wild-type cells was completely abolished in Rad51C- or Rad51D-deficient cells, but near normal in Fancg/xrcc9 cells. In marked contrast, very high levels of SCEs were observed in DNA-PKcs-null, DNA-PKcs kinase-dead and Ku80-null mutants. SCE induction was also abolished in T2609 cluster mutant cells, but was only slightly reduced in the S2056 cluster mutant cells. Since both non-homologous end-joining (NHEJ) and HRR systems utilize initial DNA lesions as a substrate, these results suggest the possibility of a competitive interference phenomenon operating between NHEJ and at least the Rad51C/D components of HRR; the level of interaction between damaged DNA and a particular DNA-PK component may determine the level of interaction of such DNA with a relevant HRR component. PMID:24714417</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21086039','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21086039"><span>Many functions of the meiotic cohesin.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Bardhan, Amit</p>
<p>2010-12-01</p>
<p>Sister chromatids are held together from the time of their formation in S phase until they segregate in anaphase by the cohesin complex. In meiosis of most organisms, the mitotic Mcd1/Scc1/Rad21 subunit of the cohesin complex is largely replaced by its paralog named Rec8. This article reviews the specialized functions of Rec8 that are crucial for diverse aspects of chromosome dynamics in meiosis, and presents some speculations relating to meiotic chromosome organization.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5027485','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5027485"><span>A defect in homologous recombination leads to increased translesion synthesis in E. coli</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Naiman, Karel; Pagès, Vincent; Fuchs, Robert P.</p>
<p>2016-01-01</p>
<p>DNA damage tolerance pathways allow cells to duplicate their genomes despite the presence of replication blocking lesions. Cells possess two major tolerance strategies, namely translesion synthesis (TLS) and homology directed gap repair (HDGR). TLS pathways involve specialized DNA polymerases that are able to synthesize past DNA lesions with an intrinsic risk of causing point mutations. In contrast, HDGR pathways are essentially error-free as they rely on the recovery of missing information from the sister chromatid by RecA-mediated homologous recombination. We have investigated the genetic control of pathway choice between TLS and HDGR in vivo in Escherichia coli. In a strain with wild type RecA activity, the extent of TLS across replication blocking lesions is generally low while HDGR is used extensively. Interestingly, recA alleles that are partially impaired in D-loop formation confer a decrease in HDGR and a concomitant increase in TLS. Thus, partial defect of RecA's capacity to invade the homologous sister chromatid increases the lifetime of the ssDNA.RecA filament, i.e. the ‘SOS signal’. This increase favors TLS by increasing both the TLS polymerase concentration and the lifetime of the TLS substrate, before it becomes sequestered by homologous recombination. In conclusion, the pathway choice between error-prone TLS and error-free HDGR is controlled by the efficiency of homologous recombination. PMID:27257075</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22819078','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22819078"><span>A single mutation in Securin induces chromosomal instability and enhances cell invasion.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Mora-Santos, Mar; Castilla, Carolina; Herrero-Ruiz, Joaquín; Giráldez, Servando; Limón-Mortés, M Cristina; Sáez, Carmen; Japón, Miguel Á; Tortolero, Maria; Romero, Francisco</p>
<p>2013-01-01</p>
<p>Pituitary tumour transforming gene (pttg1) encodes Securin, a protein involved in the inhibition of sister chromatid separation binding to Separase until the onset of anaphase. Separase is a cysteine-protease that degrades cohesin to segregate the sister chromatids to opposite poles of the cell. The amount of Securin is strongly regulated because it should allow Separase activation when it is degraded by the anaphase promoting complex/cyclosome, should arrest the cell cycle after DNA damage, when it is degraded through SKP1-CUL1-βTrCP ubiquitin ligase, and its overexpression induces tumour formation and correlates with metastasis in multiple tumours. Securin is a phosphoprotein that contains 32 potentially phosphorylatable residues. We mutated and analysed most of them, and found a single mutant, hSecT60A, that showed enhanced oncogenic properties. Our fluorescence activated cell sorting analysis, fluorescence in situ hybridisation assays, tumour cell migration and invasion experiments and gene expression by microarrays analysis clearly involved hSecT60A in chromosomal instability and cell invasion. These results show, for the first time, that a single mutation in pttg1 is sufficient to trigger the oncogenic properties of Securin. The finding of this point mutation in patients might be used as an effective strategy for early detection of cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=20040173044&hterms=Culture+differences&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D90%26Ntt%3DCulture%2Bdifferences','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=20040173044&hterms=Culture+differences&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D90%26Ntt%3DCulture%2Bdifferences"><span>Radiation-induced chromosomal instability in BALB/c and C57BL/6 mice: the difference is as clear as black and white</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p>
<p>Ponnaiya, B.; Cornforth, M. N.; Ullrich, R. L.</p>
<p>1997-01-01</p>
<p>Genomic instability has been proposed to be the earliest step in radiation-induced tumorigenesis. It follows from this hypothesis that individuals highly susceptible to induction of tumors by radiation should exhibit enhanced radiation-induced instability. BALB/c white mice are considerably more sensitive to radiation-induced mammary cancer than C57BL/6 black mice. In this study, primary mammary epithelial cell cultures from these two strains were examined for the "delayed" appearance of chromosomal aberrations after exposure to 137Cs gamma radiation, as a measure of radiation-induced genomic instability. As expected, actively dividing cultures from both strains showed a rapid decline of initial asymmetrical aberrations with time postirradiation. However, after 16 population doublings, cells from BALB/c mice exhibited a marked increase in the frequency of chromatid-type breaks and gaps which remained elevated throughout the time course of the experiment (28 doublings). No such effect was observed for the cells of C57BL/6 mice; after the rapid clearance of initial aberrations, the frequency of chromatid-type aberrations in the irradiated population remained at or near those of nonirradiated controls. These results demonstrate a correlation between the latent expression of chromosomal damage in vitro and susceptibility for mammary tumors, and provide further support for the central role of radiation-induced instability in the process of tumorigenesis.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28514186','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28514186"><span>APC/C-Cdc20 mediates deprotection of centromeric cohesin at meiosis II in yeast.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Jonak, Katarzyna; Zagoriy, Ievgeniia; Oz, Tugce; Graf, Peter; Rojas, Julie; Mengoli, Valentina; Zachariae, Wolfgang</p>
<p>2017-06-18</p>
<p>Cells undergoing meiosis produce haploid gametes through one round of DNA replication followed by 2 rounds of chromosome segregation. This requires that cohesin complexes, which establish sister chromatid cohesion during S phase, are removed in a stepwise manner. At meiosis I, the separase protease triggers the segregation of homologous chromosomes by cleaving cohesin's Rec8 subunit on chromosome arms. Cohesin persists at centromeres because the PP2A phosphatase, recruited by the shugoshin protein, dephosphorylates Rec8 and thereby protects it from cleavage. While chromatids disjoin upon cleavage of centromeric Rec8 at meiosis II, it was unclear how and when centromeric Rec8 is liberated from its protector PP2A. One proposal is that bipolar spindle forces separate PP2A from Rec8 as cells enter metaphase II. We show here that sister centromere biorientation is not sufficient to "deprotect" Rec8 at meiosis II in yeast. Instead, our data suggest that the ubiquitin-ligase APC/C Cdc20 removes PP2A from centromeres by targeting for degradation the shugoshin Sgo1 and the kinase Mps1. This implies that Rec8 remains protected until entry into anaphase II when it is phosphorylated concurrently with the activation of separase. Here, we provide further support for this model and speculate on its relevance to mammalian oocytes.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5499901','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5499901"><span>APC/C-Cdc20 mediates deprotection of centromeric cohesin at meiosis II in yeast</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Jonak, Katarzyna; Oz, Tugce; Graf, Peter; Rojas, Julie; Mengoli, Valentina; Zachariae, Wolfgang</p>
<p>2017-01-01</p>
<p>ABSTRACT Cells undergoing meiosis produce haploid gametes through one round of DNA replication followed by 2 rounds of chromosome segregation. This requires that cohesin complexes, which establish sister chromatid cohesion during S phase, are removed in a stepwise manner. At meiosis I, the separase protease triggers the segregation of homologous chromosomes by cleaving cohesin's Rec8 subunit on chromosome arms. Cohesin persists at centromeres because the PP2A phosphatase, recruited by the shugoshin protein, dephosphorylates Rec8 and thereby protects it from cleavage. While chromatids disjoin upon cleavage of centromeric Rec8 at meiosis II, it was unclear how and when centromeric Rec8 is liberated from its protector PP2A. One proposal is that bipolar spindle forces separate PP2A from Rec8 as cells enter metaphase II. We show here that sister centromere biorientation is not sufficient to “deprotect” Rec8 at meiosis II in yeast. Instead, our data suggest that the ubiquitin-ligase APC/CCdc20 removes PP2A from centromeres by targeting for degradation the shugoshin Sgo1 and the kinase Mps1. This implies that Rec8 remains protected until entry into anaphase II when it is phosphorylated concurrently with the activation of separase. Here, we provide further support for this model and speculate on its relevance to mammalian oocytes. PMID:28514186</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26694509','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26694509"><span>Meiosis.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Hillers, Kenneth J; Jantsch, Verena; Martinez-Perez, Enrique; Yanowitz, Judith L</p>
<p>2017-05-04</p>
<p>Sexual reproduction requires the production of haploid gametes (sperm and egg) with only one copy of each chromosome; fertilization then restores the diploid chromosome content in the next generation. This reduction in genetic content is accomplished during a specialized cell division called meiosis, in which two rounds of chromosome segregation follow a single round of DNA replication. In preparation for the first meiotic division, homologous chromosomes pair and synapse, creating a context that promotes formation of crossover recombination events. These crossovers, in conjunction with sister chromatid cohesion, serve to connect the two homologs and facilitate their segregation to opposite poles during the first meiotic division. During the second meiotic division, which is similar to mitosis, sister chromatids separate; the resultant products are haploid cells that become gametes. In Caenorhabditis elegans (and most other eukaryotes) homologous pairing and recombination are required for proper chromosome inheritance during meiosis; accordingly, the events of meiosis are tightly coordinated to ensure the proper execution of these events. In this chapter, we review the seminal events of meiosis: pairing of homologous chromosomes, the changes in chromosome structure that chromosomes undergo during meiosis, the events of meiotic recombination, the differentiation of homologous chromosome pairs into structures optimized for proper chromosome segregation at Meiosis I, and the ultimate segregation of chromosomes during the meiotic divisions. We also review the regulatory processes that ensure the coordinated execution of these meiotic events during prophase I.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/7168826','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/7168826"><span>Cyclophosphamide induced in vivo sister chromatid exchanges (SCE) in Mus musculus. I: Strain differences and empirical association with relative chromosome size.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Reimer, D L; Singh, S M</p>
<p>1982-01-01</p>
<p>The inducibility of sister chromatid exchanges (SCEs) by cyclophosphamide (CP) in bone marrow cells was evaluated in vivo in the three genetic strains of mice (C3H/s, C57BL/6J, and Balb/c). Female mice (10 to 12 wks old, mean = 22.9g, SD = 3.2g) were administered with nine hourly injections of 214.19 mg/kg 5-Bromo-2' deoxyuridine (BrdU) followed by 0, 0.048, 0.449, 4.585 or 46.93 mg/kg CP and 4 mg/kg colcemid. SCEs were evaluated following differential staining procedures of Perry and Wolff (1974). The base-line SCEs were similar in all strains with about ten SCEs/cell. Increasing CP concentrations yielded an increased level of SCEs. Most cells showed extensive damage in CP doses exceeding 4.55 mg/kg. No SCE evaluation was possible beyond this concentration. Strain differences were evident at every dose of CP, and Balb/c was the least susceptible strain to SCE induction. F1 hybrids involving C3H/s female and Balb/c male showed SCE values closer to Balb/c. Data on the association between chromosome length and frequency of SCEs are provided. They empirically establish a positive correlation (r = 0.90) between the two features. Most induced SCEs were interstitially located rather than terminally positioned on the chromosome.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/3724775','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/3724775"><span>Very low sister-chromatid exchange rate in Seventh-Day Adventists.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Wulf, H C; Iversen, A S; Husum, B; Niebuhr, E</p>
<p>1986-08-01</p>
<p>42 Seventh-Day Adventists (SDAs) and 42 controls matched for sex, age and occupation had their sister-chromatid exchange (SCE) examined in peripheral blood lymphocytes. This was done to examine if the SCE frequency was lower in this group of people, who are known to have a decreased cancer risk compared to the general population. The average SCE/cell in 30 cells from each person was 5.54 +/- 0.07 (mean +/- standard error of the mean) for the SDAs and 8.00 +/- 0.15 for the controls, the difference being statistically significant (p less than 0.00001). No difference in SCE frequency was found between SDAs eating only an ovo-lacto-vegetarian diet and those eating some fish or meat. The mitotic index (MI) was significantly higher and the replication index (RI) was significantly lower in SDAs than in controls. No correlation was found between gamma (a statistical transformation of SCEs/cell) and MI or RI within the groups of SDAs or controls. In the pooled data there was a negative correlation of gamma and MI and a positive correlation of gamma and RI. Of the interpersonal variation in gamma 8% and 14% could be explained by MI and RI. The finding of a lower SCE frequency in a group of SDAs who have a low risk of cancer might indirectly indicate a relation between SCE and cancer and encourages further studies of SCE and diet.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25009111','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25009111"><span>The mitosis-regulating and protein-protein interaction activities of astrin are controlled by aurora-A-induced phosphorylation.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Chiu, Shao-Chih; Chen, Jo-Mei Maureen; Wei, Tong-You Wade; Cheng, Tai-Shan; Wang, Ya-Hui Candice; Ku, Chia-Feng; Lian, Chiao-Hsuan; Liu, Chun-Chih Jared; Kuo, Yi-Chun; Yu, Chang-Tze Ricky</p>
<p>2014-09-01</p>
<p>Cells display dramatic morphological changes in mitosis, where numerous factors form regulatory networks to orchestrate the complicated process, resulting in extreme fidelity of the segregation of duplicated chromosomes into two daughter cells. Astrin regulates several aspects of mitosis, such as maintaining the cohesion of sister chromatids by inactivating Separase and stabilizing spindle, aligning and segregating chromosomes, and silencing spindle assembly checkpoint by interacting with Src kinase-associated phosphoprotein (SKAP) and cytoplasmic linker-associated protein-1α (CLASP-1α). To understand how Astrin is regulated in mitosis, we report here that Astrin acts as a mitotic phosphoprotein, and Aurora-A phosphorylates Astrin at Ser(115). The phosphorylation-deficient mutant Astrin S115A abnormally activates spindle assembly checkpoint and delays mitosis progression, decreases spindle stability, and induces chromosome misalignment. Mechanistic analyses reveal that Astrin phosphorylation mimicking mutant S115D, instead of S115A, binds and induces ubiquitination and degradation of securin, which sequentially activates Separase, an enzyme required for the separation of sister chromatids. Moreover, S115A fails to bind mitosis regulators, including SKAP and CLASP-1α, which results in the mitotic defects observed in Astrin S115A-transfected cells. In conclusion, Aurora-A phosphorylates Astrin and guides the binding of Astrin to its cellular partners, which ensures proper progression of mitosis. Copyright © 2014 the American Physiological Society.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2910038','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2910038"><span>Evidence that MEK1 positively promotes interhomologue double-strand break repair</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Terentyev, Yaroslav; Johnson, Rebecca; Neale, Matthew J.; Khisroon, Muhammad; Bishop-Bailey, Anna; Goldman, Alastair S. H.</p>
<p>2010-01-01</p>
<p>During meiosis there is an imperative to create sufficient crossovers for homologue segregation. This can be achieved during repair of programmed DNA double-strand breaks (DSBs), which are biased towards using a homologue rather than sister chromatid as a repair template. Various proteins contribute to this bias, one of which is a meiosis specific kinase Mek1. It has been proposed that Mek1 establishes the bias by creating a barrier to sister chromatid repair, as distinct from enforcing strand invasion with the homologue. We looked for evidence that Mek1 positively stimulates strand invasion of the homologue. This was done by analysing repair of DSBs induced by the VMA1-derived endonuclease (VDE) and flanked by directly repeated sequences that can be used for intrachromatid single-strand annealing (SSA). SSA competes with interhomologue strand invasion significantly more successfully when Mek1 function is lost. We suggest the increase in intrachromosomal SSA reflects an opportunistic default repair pathway due to loss of a MEK1 stimulated bias for strand invasion of the homologous chromosome. Making use of an inhibitor sensitive mek1-as1 allele, we found that Mek1 function influences the repair pathway throughout the first4–5 h of meiosis. Perhaps reflecting a particular need to create bias for successful interhomologue events before chromosome pairing is complete. PMID:20223769</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=20040087689&hterms=gamma+ray+irradiation&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D20%26Ntt%3Dgamma%2Bray%2Birradiation','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=20040087689&hterms=gamma+ray+irradiation&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D20%26Ntt%3Dgamma%2Bray%2Birradiation"><span>Induction of genomic instability in TK6 human lymphoblasts exposed to 137Cs gamma radiation: comparison to the induction by exposure to accelerated 56Fe particles</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p>
<p>Evans, Helen H.; Horng, Min-Fen; Ricanati, Marlene; Diaz-Insua, M.; Jordan, Robert; Schwartz, Jeffrey L.</p>
<p>2003-01-01</p>
<p>The induction of genomic instability in TK6 human lymphoblasts by exposure to (137)Cs gamma radiation was investigated by measuring the frequency and characteristics of unstable clones isolated approximately 36 generations after exposure. Clones surviving irradiation and control clones were analyzed for 17 characteristics including chromosomal aberrations, growth defects, alterations in response to a second irradiation, and mutant frequencies at the thymidine kinase and Na(+)/K(+) ATPase loci. Putative unstable clones were defined as those that exhibited a significant alteration in one or more characteristics compared to the controls. The frequency and characteristics of the unstable clones were compared in clones exposed to (137)Cs gamma rays or (56)Fe particles. The majority of the unstable clones isolated after exposure to either gamma rays or (56)Fe particles exhibited chromosomal instability. Alterations in growth characteristics, radiation response and mutant frequencies occurred much less often than cytogenetic alterations in these unstable clones. The frequency and complexity of the unstable clones were greater after exposure to (56)Fe particles than to gamma rays. Unstable clones that survived 36 generations after exposure to gamma rays exhibited increases in the incidence of dicentric chromosomes but not of chromatid breaks, whereas unstable clones that survived 36 generations after exposure to (56)Fe particles exhibited increases in both chromatid and chromosome aberrations.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/servlets/purl/6661008','SCIGOV-STC'); return false;" href="https://www.osti.gov/servlets/purl/6661008"><span></span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Harrison, F.L.; Rice, D.W. Jr.; Moore, D.H.</p>
<p></p>
<p>Traditional bioassays are unsuitable for assessing sublethal effects of low levels of radioactivity because mortality and phenotypic responses are not anticipated. We compared the usefulness of chromosomal aberration (CA) and sister chromatid exchange (SCE) induction as measures of low-level radiation effects in a sediment-dwelling marine worm, Neanthes arenaceodentata. Newly hatched larvae were exposed to two radiation exposure regimes. Groups of 100 larvae were exposed to either x rays delivered at high dose rates (0.7 Gy min/sup -1/) or to /sup 60/Co gamma rays delivered at low dose rates (4.8 X 10/sup -5/ to 1.2 X 10/sup -1/ Gy h/sup -1/).more » After irradiation, the larvae were exposed to 3 X 10/sup -5/M bromodeoxyuridine (BrdUrd) for 28 h (x-ray-irradiated larvae) or for 54 h (/sup 60/Co-irradiated larvae). Slides of larval cells were prepared for observation of CAs and SCEs. Frequencies of CAs were determined in first division cells; frequencies of SCEs were determined in second division cells. Results from x-ray irradiation indicated that dose-related increases occur in chromosome and chromatid deletions, but an x-ray dose greater than or equal to 2 Gy was required to observe a significant increase. Worm larvae receiving /sup 60/Co irradiation showed elevated SCE frequencies; a significant increase in SCE frequency was observed at 0.6 Gy. 49 references, 2 figures.« less</p>
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<ol class="result-class" start="221">
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28819029','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28819029"><span>Loss of Tumor Suppressor STAG2 Promotes Telomere Recombination and Extends the Replicative Lifespan of Normal Human Cells.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Daniloski, Zharko; Smith, Susan</p>
<p>2017-10-15</p>
<p>Sister chromatids are held together by cohesin, a tripartite ring with a peripheral SA1/2 subunit, where SA1 is required for telomere cohesion and SA2 for centromere cohesion. The STAG2 gene encoding SA2 is often inactivated in human cancer, but not in in a manner associated with aneuploidy. Thus, how these tumors maintain chromosomal cohesion and how STAG2 loss contributes to tumorigenesis remain open questions. Here we show that, despite a loss in centromere cohesion, sister chromatids in STAG2 mutant tumor cells maintain cohesion in mitosis at chromosome arms and telomeres. Telomere maintenance in STAG2 mutant tumor cells occurred by either telomere recombination or telomerase activation mechanisms. Notably, these cells were refractory to telomerase inhibitors, indicating recombination can provide an alternative means of telomere maintenance. STAG2 silencing in normal human cells that lack telomerase led to increased recombination at telomeres, delayed telomere shortening, and postponed senescence onset. Insofar as telomere shortening and replicative senescence prevent genomic instability and cancer by limiting the number of cell divisions, our findings suggest that extending the lifespan of normal human cells due to inactivation of STAG2 could promote tumorigenesis by extending the period during which tumor-driving mutations occur. Cancer Res; 77(20); 5530-42. ©2017 AACR . ©2017 American Association for Cancer Research.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29792816','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29792816"><span>The Physics of the Metaphase Spindle.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Oriola, David; Needleman, Daniel J; Brugués, Jan</p>
<p>2018-05-20</p>
<p>The assembly of the mitotic spindle and the subsequent segregation of sister chromatids are based on the self-organized action of microtubule filaments, motor proteins, and other microtubule-associated proteins, which constitute the fundamental force-generating elements in the system. Many of the components in the spindle have been identified, but until recently it remained unclear how their collective behaviors resulted in such a robust bipolar structure. Here, we review the current understanding of the physics of the metaphase spindle that is only now starting to emerge.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/8186767','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/8186767"><span>In vitro studies on chemoprotective effect of Purnark against benzo(a)pyrene-induced chromosomal damage in human lymphocytes.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Ghaisas, S D; Bhide, S V</p>
<p>1994-01-01</p>
<p>Human lymphocytes were used as an assay system to test chemopreventive activity of natural products. Purnark, a mixture of extracts of turmeric, betel leaf and catechu, was tested for its chemoprotective activity against BP induced DNA damage. Sister chromatid exchange and micronuclei were used as markers to assess the protective activity of Purnark. Purnark gave 50-60% protection against BP induced SCEs and micronuclei. Purnark at 100 micrograms dose did not show any genotoxicity.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2106708','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2106708"><span>STRANDEDNESS OF VICIA FABA CHROMOSOMES AS REVEALED BY ENZYME DIGESTION STUDIES</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Trosko, James E.; Wolff, Sheldon</p>
<p>1965-01-01</p>
<p>Chromosomes and nuclei isolated from neutral formalin-fixed Vicia faba lateral roots were treated with trypsin, pepsin, RNase, or DNase. Only trypsin affected the morphology of the chromosomes and nuclei. The appearance of the chromosomes after trypsin digestion indicated that each chromatid contained four strands that could be seen with an ordinary light microscope. The experiments are interpreted as indicating that mitotic chromosomes of Vicia faba are multistranded and that the linear continuity of the chromosome is dependent on protein. PMID:5323605</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('http://www.dtic.mil/docs/citations/ADA202780','DTIC-ST'); return false;" href="http://www.dtic.mil/docs/citations/ADA202780"><span>Effects of Simultaneous Radiofrequency Radiation and Chemical Exposure of Mammalian Cells. Volume 2</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.dtic.mil/">DTIC Science & Technology</a></p>
<p></p>
<p>1988-07-01</p>
<p>chromosome - - - - - - -I aberrations and sister chromatid exchanges (SCE). Yao (1982) exposed rat kangaroo RH5 and RH1l6 cells to 2.45 GHz radiation, and...control was reported in chromosome aberrations. Yac (1982) investigated the cytogenetic consequences of chronic microwave exposure on rat kangaroo RH5...was said to be 280C. The cells were exposed both as conidia, which are "rather inactive metabolically ," and also after DNA replication had been</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28060322','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28060322"><span>Analysis of the Ambient Particulate Matter-induced Chromosomal Aberrations Using an In Vitro System.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Miousse, Isabelle R; Koturbash, Igor; Chalbot, Marie-Cécile; Hauer-Jensen, Martin; Kavouras, Ilias; Pathak, Rupak</p>
<p>2016-12-21</p>
<p>Exposure to particulate matter (PM) is a major world health concern, which may damage various cellular components, including the nuclear genetic material. To assess the impact of PM on nuclear genetic integrity, structural chromosomal aberrations are scored in the metaphase spreads of mouse RAW264.7 macrophage cells. PM is collected from ambient air with a high volume total suspended particles sampler. The collected material is solubilized and filtered to retain the water-soluble, fine portion. The particles are characterized for chemical composition by nuclear magnetic resonance (NMR) spectroscopy. Different concentrations of particle suspension are added onto an in vitro culture of RAW264.7 mouse macrophages for a total exposure time of 72 hr, along with untreated control cells. At the end of exposure, the culture is treated with colcemid to arrest cells in metaphase. Cells are then harvested, treated with hypotonic solution, fixed in acetomethanol, dropped onto glass slides and finally stained with Giemsa solution. Slides are examined to assess the structural chromosomal aberrations (CAs) in metaphase spreads at 1,000X magnification using a bright-field microscope. 50 to 100 metaphase spread are scored for each treatment group. This technique is adapted for the detection of structural chromosomal aberrations (CAs), such as chromatid-type breaks, chromatid-type exchanges, acentric fragments, dicentric and ring chromosomes, double minutes, endoreduplication, and Robertsonian translocations in vitro after exposure to PM. It is a powerful method to associate a well-established cytogenetic endpoint to epigenetic alterations.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4041417','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4041417"><span>Histone H3 K79 methylation states play distinct roles in UV-induced sister chromatid exchange and cell cycle checkpoint arrest in Saccharomyces cerevisiae</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Rossodivita, Alyssa A.; Boudoures, Anna L.; Mecoli, Jonathan P.; Steenkiste, Elizabeth M.; Karl, Andrea L.; Vines, Eudora M.; Cole, Arron M.; Ansbro, Megan R.; Thompson, Jeffrey S.</p>
<p>2014-01-01</p>
<p>Histone post-translational modifications have been shown to contribute to DNA damage repair. Prior studies have suggested that specific H3K79 methylation states play distinct roles in the response to UV-induced DNA damage. To evaluate these observations, we examined the effect of altered H3K79 methylation patterns on UV-induced G1/S checkpoint response and sister chromatid exchange (SCE). We found that the di- and trimethylated states both contribute to activation of the G1/S checkpoint to varying degrees, depending on the synchronization method, although methylation is not required for checkpoint in response to high levels of UV damage. In contrast, UV-induced SCE is largely a product of the trimethylated state, which influences the usage of gene conversion versus popout mechanisms. Regulation of H3K79 methylation by H2BK123 ubiquitylation is important for both checkpoint function and SCE. H3K79 methylation is not required for the repair of double-stranded breaks caused by transient HO endonuclease expression, but does play a modest role in survival from continuous exposure. The overall results provide evidence for the participation of H3K79 methylation in UV-induced recombination repair and checkpoint activation, and further indicate that the di- and trimethylation states play distinct roles in these DNA damage response pathways. PMID:24748660</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2391130','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2391130"><span>Chromosomal radiosensitivity in head and neck cancer patients: evidence for genetic predisposition?</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>De Ruyck, K; de Gelder, V; Van Eijkeren, M; Boterberg, T; De Neve, W; Vral, A; Thierens, H</p>
<p>2008-01-01</p>
<p>The association between chromosomal radiosensitivity and genetic predisposition to head and neck cancer was investigated in this study. In all, 101 head and neck cancer patients and 75 healthy control individuals were included in the study. The G2 assay was used to measure chromosomal radiosensitivity. The results demonstrated that head and neck cancer patients had a statistically higher number of radiation-induced chromatid breaks than controls, with mean values of 1.23 and 1.10 breaks per cell, respectively (P<0.001). Using the 90th percentile of the G2 scores of the healthy individuals as a cutoff value for chromosomal radiosensitivity, 26% of the cancer patients were radiosensitive compared with 9% of the healthy controls (P=0.008). The mean number of radiation-induced chromatid breaks and the proportion of radiosensitive individuals were highest for oral cavity cancer patients (1.26 breaks per cell, 38%) and pharynx cancer patients (1.27 breaks per cell, 35%). The difference between patients and controls was most pronounced in the lower age group (⩽50 years, 1.32 breaks per cell, 38%) and in the non- and light smoking patient group (⩽10 pack-years, 1.28 breaks per cell, 46%). In conclusion, enhanced chromosomal radiosensitivity is a marker of genetic predisposition to head and neck cancer, and the genetic contribution is highest for oral cavity and pharynx cancer patients and for early onset and non- and light smoking patients. PMID:18414410</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26207596','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26207596"><span>Baseline frequency of chromosomal aberrations and sister chromatid exchanges in peripheral blood lymphocytes of healthy individuals living in Turin (North-Western Italy): assessment of the effects of age, sex and GSTs gene polymorphisms on the levels of genomic damage.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Santovito, Alfredo; Cervella, Piero; Delpero, Massimiliano</p>
<p>2016-05-01</p>
<p>The increased exposure to environmental pollutants has led to the awareness of the necessity for constant monitoring of human populations, especially those living in urban areas. This study evaluated the background levels of genomic damage in a sample of healthy subjects living in the urban area of Turin (Italy). The association between DNA damage with age, sex and GSTs polymorphisms was assessed. One hundred and one individuals were randomly sampled. Sister Chromatid Exchanges (SCEs) and Chromosomal Aberrations (CAs) assays, as well as genotyping of GSTT1 and GSTM1 genes, were performed. Mean values of SCEs and CAs were 5.137 ± 0.166 and 0.018 ± 0.002, respectively. Results showed age and gender associated with higher frequencies of these two cytogenetic markers. The eldest subjects (51-65 years) showed significantly higher levels of genomic damage than younger individuals. GSTs polymorphisms did not appear to significantly influence the frequencies of either markers. The CAs background frequency observed in this study is one of the highest reported among European populations. Turin is one of the most polluted cities in Europe in terms of air fine PM10 and ozone and the clastogenic potential of these pollutants may explain the high frequencies of chromosomal rearrangements reported here.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2010Nanot..21c5102P','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2010Nanot..21c5102P"><span>Nanoceria have no genotoxic effect on human lens epithelial cells</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p>
<p>Pierscionek, Barbara K.; Li, Yuebin; Yasseen, Akeel A.; Colhoun, Liza M.; Schachar, Ronald A.; Chen, Wei</p>
<p>2010-01-01</p>
<p>There are no treatments for reversing or halting cataract, a disease of the structural proteins in the eye lens, that has associations with other age-related degenerative conditions such as Alzheimer's disease. The incidence of cataract and associated conditions is increasing as the average age of the population rises. Protein folding diseases are difficult to assess in vivo as proteins and their age-related changes are assessed after extraction. Nanotechnology can be used to investigate protein changes in the intact lens as well as for a potential means of drug delivery. Nanoparticles, such as cerium oxide (CeO2) which have antioxidant properties, may even be used as a means of treating cataract directly. Prior to use in treatments, nanoparticle genotoxicity must be tested to assess the extent of any DNA or chromosomal damage. Sister chromatid exchanges were measured and DNA damage investigated using the alkaline COMET assay on cultured human lens epithelial cells, exposed to 5 and 10 µg ml-1 of CeO2 nanoparticles (nanoceria). Nanoceria at these dosages did not cause any DNA damage or significant increases in the number of sister chromatid exchanges. The absence of genotoxic effects on lens cells suggests that nanoceria, in the doses and exposures tested in this study, are not deleterious to the eye lens and have the potential for use in studying structural alterations, in developing non-surgical cataract treatments and in investigating other protein folding diseases.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11406183','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11406183"><span>Differences in sensitivity of murine spermatogonia and somatic cells in vivo to sister-chromatid exchange induction by nitrosoureas.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Morales-Ramírez, P; Cruz-Vallejo, V; Rodríguez-Reyes, R</p>
<p>2001-07-01</p>
<p>Previously published data indicate that spermatogonia (SPG) are less sensitive to a sister-chromatid exchange (SCE) induction for different mutagens. In an earlier study, we have observed that bromodeoxyuridine (BrdU) substituted murine SPG are less sensitive to SCE induction by gamma ray in cells, than bone marrow (BM) and salivary gland (SG) cells in vivo. This was interpreted to mean that SPG are more efficient in DNA repair or are less prone to SCE induction. That the lower induction of SCE could be due to a reduced accessibility of mutagens to the SPG by virtue of a physiological barrier, was discarded by using gamma radiation. The aim of the present study was to establish whether or not there are differences in SCE induction by nitrosoureas among SPG, SG and BM cells with BrdU substituted or unsubstituted DNA. It was observed that SCE induction by methylnitrosourea (MNU) or by ethylnitrosourea (ENU) in SPG was, respectively, five and two times lower than in SG, and ten and three times lower than in BM. In SPG after BrdU incorporation, there was no increase in efficiency of SCE induction; in fact, there was even a slight decrease by exposure to MNU or ENU. BM and SG cells showed an increased efficiency in SCE induction after BrdU incorporation. This implies that SPG are also less sensitive to SCE induction by nitrosoureas, which cause a different kind of damage from previously assayed mutagens.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11746029','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11746029"><span>Cancer-prone syndrome of mosaic variegated aneuploidy and total premature chromatid separation: report of five infants.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Kajii, T; Ikeuchi, T; Yang, Z Q; Nakamura, Y; Tsuji, Y; Yokomori, K; Kawamura, M; Fukuda, S; Horita, S; Asamoto, A</p>
<p>2001-11-15</p>
<p>Five infants (two girls and three boys) from four families all had severe pre- and postnatal growth retardation, profound developmental delay, microcephaly, hypoplasia of the brain with Dandy-Walker complex or other posterior fossa malformations, and developed uncontrollable clonic seizures. Four infants developed Wilms tumors, and one showed cystic lesions in bilateral kidneys. All five infants showed variegated mosaic aneuploidy in cultured lymphocytes. In two infants whose chromosomes were prepared by us, 48.5%-83.2% lymphocytes showed total premature chromatid separation (PCS). Their parents had 3.5%-41.7% of their lymphocytes in total PCS. The remaining three infants and their parents, whose chromosomes were prepared at outside laboratories, tended to show lower frequencies of total PCS. Another five infants reported with the disorder were reviewed together with the five infants we described. Together, their clinical and cytogenetic manifestations were similar enough to suggest a syndrome. Seven of the 10 infants developed proven or probable Wilms tumors. The age at diagnosis of the tumors was younger than usual at 2-16 months. The tumors were bilateral in four infants and unilateral in three infants, and cystic changes were present in six infants. Two infants developed botryoid rhabdomyosarcoma. The carriers of the syndrome are thus liable to tumorigenesis. The possible role of mitotic checkpoint defects, proven in two infants with the syndrome (Matsuura et al. [2000: Am J Hum Genet 69:483-486]), was discussed in connection with tumor development and progression. Copyright 2001 Wiley-Liss, Inc.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3389968','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3389968"><span>Ribosomal DNA Organization Before and After Magnification in Drosophila melanogaster</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Bianciardi, Alessio; Boschi, Manuela; Swanson, Ellen E.; Belloni, Massimo; Robbins, Leonard G.</p>
<p>2012-01-01</p>
<p>In all eukaryotes, the ribosomal RNA genes are stably inherited redundant elements. In Drosophila melanogaster, the presence of a Ybb− chromosome in males, or the maternal presence of the Ribosomal exchange (Rex) element, induces magnification: a heritable increase of rDNA copy number. To date, several alternative classes of mechanisms have been proposed for magnification: in situ replication or extra-chromosomal replication, either of which might act on short or extended strings of rDNA units, or unequal sister chromatid exchange. To eliminate some of these hypotheses, none of which has been clearly proven, we examined molecular-variant composition and compared genetic maps of the rDNA in the bb2 mutant and in some magnified bb+ alleles. The genetic markers used are molecular-length variants of IGS sequences and of R1 and R2 mobile elements present in many 28S sequences. Direct comparison of PCR products does not reveal any particularly intensified electrophoretic bands in magnified alleles compared to the nonmagnified bb2 allele. Hence, the increase of rDNA copy number is diluted among multiple variants. We can therefore reject mechanisms of magnification based on multiple rounds of replication of short strings. Moreover, we find no changes of marker order when pre- and postmagnification maps are compared. Thus, we can further restrict the possible mechanisms to two: replication in situ of an extended string of rDNA units or unequal exchange between sister chromatids. PMID:22505623</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4224182','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4224182"><span>Sisters Unbound Is Required for Meiotic Centromeric Cohesion in Drosophila melanogaster</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Krishnan, Badri; Thomas, Sharon E.; Yan, Rihui; Yamada, Hirotsugu; Zhulin, Igor B.; McKee, Bruce D.</p>
<p>2014-01-01</p>
<p>Regular meiotic chromosome segregation requires sister centromeres to mono-orient (orient to the same pole) during the first meiotic division (meiosis I) when homologous chromosomes segregate, and to bi-orient (orient to opposite poles) during the second meiotic division (meiosis II) when sister chromatids segregate. Both orientation patterns require cohesion between sister centromeres, which is established during meiotic DNA replication and persists until anaphase of meiosis II. Meiotic cohesion is mediated by a conserved four-protein complex called cohesin that includes two structural maintenance of chromosomes (SMC) subunits (SMC1 and SMC3) and two non-SMC subunits. In Drosophila melanogaster, however, the meiotic cohesion apparatus has not been fully characterized and the non-SMC subunits have not been identified. We have identified a novel Drosophila gene called sisters unbound (sunn), which is required for stable sister chromatid cohesion throughout meiosis. sunn mutations disrupt centromere cohesion during prophase I and cause high frequencies of non-disjunction (NDJ) at both meiotic divisions in both sexes. SUNN co-localizes at centromeres with the cohesion proteins SMC1 and SOLO in both sexes and is necessary for the recruitment of both proteins to centromeres. Although SUNN lacks sequence homology to cohesins, bioinformatic analysis indicates that SUNN may be a structural homolog of the non-SMC cohesin subunit stromalin (SA), suggesting that SUNN may serve as a meiosis-specific cohesin subunit. In conclusion, our data show that SUNN is an essential meiosis-specific Drosophila cohesion protein. PMID:25194162</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11948630','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11948630"><span>Low frequency noise and whole-body vibration cause increased levels of sister chromatid exchange in splenocytes of exposed mice.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Silva, M J; Dias, A; Barreta, A; Nogueira, P J; Castelo-Branco, N A A; Boavida, M G</p>
<p>2002-01-01</p>
<p>Chronic exposure to low frequency (LF) noise and whole-body vibration (WBV) induces both physiological and psychological alterations in man. Recently, we have shown that long-term occupational exposure to LF noise and WBV produces genotoxic effects in man expressed as an increase in sister chromatid exchange (SCE) levels in lymphocytes. The objectives of the present study were to investigate whether the observed effect could be reproduced in a murine model and, if so, which of the agents, LF noise alone or in combination with WBV, would be instrumental in the SCE induction. SCEs were analyzed in spleen lymphocytes of mice exposed to LF noise alone and in combination with WBV for 300 and 600 hr. An effect at the cell cycle kinetics level was also investigated. The results revealed significant increases in the mean SCE number per cell and in the proportion of cells with high frequency of SCEs (HFCs) in lymphocytes of mice submitted to combined noise and WBV over controls. No significant differences were found between single noise-exposed and control mice. A cell cycle delay was observed exclusively in the noise and WBV exposure groups. In conclusion, we demonstrated that, as in exposed workers, prolonged exposure to the combination of LF noise and WBV determines an increase in SCE level in mice while LF noise alone is not effective in SCE induction. Copyright 2002 Wiley-Liss, Inc.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21537955','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21537955"><span>The in vitro MN assay in 2011: origin and fate, biological significance, protocols, high throughput methodologies and toxicological relevance.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Kirsch-Volders, Micheline; Plas, Gina; Elhajouji, Azeddine; Lukamowicz, Magdalena; Gonzalez, Laetitia; Vande Loock, Kim; Decordier, Ilse</p>
<p>2011-08-01</p>
<p>Micronuclei (MN) are small, extranuclear bodies that arise in dividing cells from acentric chromosome/chromatid fragments or whole chromosomes/chromatids lagging behind in anaphase and are not included in the daughter nuclei at telophase. The mechanisms of MN formation are well understood; their possible postmitotic fate is less evident. The MN assay allows detection of both aneugens and clastogens, shows simplicity of scoring, is widely applicable in different cell types, is internationally validated, has potential for automation and is predictive for cancer. The cytokinesis-block micronucleus assay (CBMN) allows assessment of nucleoplasmic bridges, nuclear buds, cell division inhibition, necrosis and apoptosis and in combination with FISH using centromeric probes, the mechanistic origin of the MN. Therefore, the CBMN test can be considered as a "cytome" assay covering chromosome instability, mitotic dysfunction, cell proliferation and cell death. The toxicological relevance of the MN test is strong: it covers several endpoints, its sensitivity is high, its predictivity for in vivo genotoxicity requires adequate selection of cell lines, its statistical power is increased by the recently available high throughput methodologies, it might become a possible candidate for replacing in vivo testing, it allows good extrapolation for potential limits of exposure or thresholds and it is traceable in experimental in vitro and in vivo systems. Implementation of in vitro MN assays in the test battery for hazard and risk assessment of potential mutagens/carcinogens is therefore fully justified.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/7593159','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/7593159"><span>A three-dimensional structural dissection of Drosophila polytene chromosomes.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Urata, Y; Parmelee, S J; Agard, D A; Sedat, J W</p>
<p>1995-10-01</p>
<p>We have analyzed the three-dimensional structural details of Drosophila melanogaster polytene chromosome bands and interbands using three-dimensional light microscopy and a novel method of sample preparation that does not involve flattening or stretching the chromosomes. Bands have been visualized in unfixed chromosomes stained with the DNA specific dye 4,6-Diamidino-2-phenylindole (DAPI). Interbands have been visualized using fixed chromosomes that have been immunostained with an antibody to RNA polymerase II. Additionally, these structures have been analyzed using in situ hybridization with probes from specific genetic loci (Notch and white). Bands are seen to be composed of approximately 36 substructural features that measure 0.2-0.4 micron in diameter. We suggest that these substructural features are in fact longitudinal fibers made up of bundles of chromatids. Band shape can be a reproducible characteristic of a particular band and is dependent on the spatial relationship of these bundles, varying from bands with a uniform distribution of bundles to bands with a peripheral concentration of chromatin. Interbands are composed of bundles of chromatids of a similar size and number as those seen in the bands. The distribution of bundles is similar between a band and the neighboring interband, implying that there is a long range organization to the DNA that includes both the coding and the noncoding portions of genes. Finally, we note that the polytene chromosome has a circular shape when viewed in cross section, whether there are one or two homologs present.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/18414410','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/18414410"><span>Chromosomal radiosensitivity in head and neck cancer patients: evidence for genetic predisposition?</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>De Ruyck, K; de Gelder, V; Van Eijkeren, M; Boterberg, T; De Neve, W; Vral, A; Thierens, H</p>
<p>2008-05-20</p>
<p>The association between chromosomal radiosensitivity and genetic predisposition to head and neck cancer was investigated in this study. In all, 101 head and neck cancer patients and 75 healthy control individuals were included in the study. The G(2) assay was used to measure chromosomal radiosensitivity. The results demonstrated that head and neck cancer patients had a statistically higher number of radiation-induced chromatid breaks than controls, with mean values of 1.23 and 1.10 breaks per cell, respectively (P<0.001). Using the 90th percentile of the G(2) scores of the healthy individuals as a cutoff value for chromosomal radiosensitivity, 26% of the cancer patients were radiosensitive compared with 9% of the healthy controls (P=0.008). The mean number of radiation-induced chromatid breaks and the proportion of radiosensitive individuals were highest for oral cavity cancer patients (1.26 breaks per cell, 38%) and pharynx cancer patients (1.27 breaks per cell, 35%). The difference between patients and controls was most pronounced in the lower age group (<or=50 years, 1.32 breaks per cell, 38%) and in the non- and light smoking patient group (<or=10 pack-years, 1.28 breaks per cell, 46%). In conclusion, enhanced chromosomal radiosensitivity is a marker of genetic predisposition to head and neck cancer, and the genetic contribution is highest for oral cavity and pharynx cancer patients and for early onset and non- and light smoking patients.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19465921','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19465921"><span>The FANC pathway and BLM collaborate during mitosis to prevent micro-nucleation and chromosome abnormalities.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Naim, Valeria; Rosselli, Filippo</p>
<p>2009-06-01</p>
<p>Loss-of-function of caretaker genes characterizes a group of cancer predisposition diseases that feature cellular hypersensitivity to DNA damage and chromosome fragility; this group includes Fanconi anaemia and Bloom syndrome. The products of the 13 FANC genes (mutated in Fanconi anaemia), which constitute the 'FANC' pathway, and BLM (the RecQ helicase mutated in Bloom syndrome) are thought to collaborate during the S phase of the cell cycle, preventing chromosome instability. Recently, BLM has been implicated in the completion of sister chromatid separation during mitosis, a complex process in which precise regulation and execution is crucial to preserve genomic stability. Here we show for the first time a role for the FANC pathway in chromosome segregation during mitotic cell division. FANCD2, a key component of the pathway, localizes to discrete spots on mitotic chromosomes. FANCD2 chromosomal localization is responsive to replicative stress and specifically targets aphidicolin (APH)-induced chromatid gaps and breaks. Our data indicate that the FANC pathway is involved in rescuing abnormal anaphase and telophase (ana-telophase) cells, limiting aneuploidy and reducing chromosome instability in daughter cells. We further address a cooperative role for the FANC pathway and BLM in preventing micronucleation, through FANC-dependent targeting of BLM to non-centromeric abnormal structures induced by replicative stress. We reveal new crosstalk between FANC and BLM proteins, extending their interaction beyond the S-phase rescue of damaged DNA to the safeguarding of chromosome stability during mitosis.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24852491','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24852491"><span>Health assessment of gasoline and fuel oxygenate vapors: micronucleus and sister chromatid exchange evaluations.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Schreiner, Ceinwen A; Hoffman, Gary M; Gudi, Ramadevi; Clark, Charles R</p>
<p>2014-11-01</p>
<p>Micronucleus and sister chromatid exchange (SCE) tests were performed for vapor condensate of baseline gasoline (BGVC), or gasoline with oxygenates, methyl tert-butyl ether (G/MTBE), ethyl tert butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), t-butyl alcohol (TBA), or ethanol (G/EtOH). Sprague Dawley rats (the same 5/sex/group for both endpoints) were exposed to 0, 2000, 10,000, or 20,000mg/m(3) of each condensate, 6h/day, 5days/week over 4weeks. Positive controls (5/sex/test) were given cyclophosphamide IP, 24h prior to sacrifice at 5mg/kg (SCE test) and 40mg/kg (micronucleus test). Blood was collected from the abdominal aorta for the SCE test and femurs removed for the micronucleus test. Blood cell cultures were treated with 5μg/ml bromodeoxyuridine (BrdU) for SCE evaluation. No significant increases in micronucleated immature erythrocytes were observed for any test material. Statistically significant increases in SCE were observed in rats given BGVC alone or in female rats given G/MTBE. G/TAME induced increased SCE in both sexes at the highest dose only. Although DNA perturbation was observed for several samples, DNA damage was not expressed as increased micronuclei in bone marrow cells. Inclusion of oxygenates in gasoline did not increase the effects of gasoline alone or produce a cytogenetic hazard. Copyright © 2014 Elsevier Inc. All rights reserved.</p>
</li>
</ol>
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<ol class="result-class" start="241">
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19500270','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19500270"><span>Micronuclear and sister chromatid exchange analyses in peripheral lymphocytes of patients with oral lichen planus--a pilot study.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Ergun, S; Warnakulasuriya, S; Duman, N; Saruhanoğlu, A; Sevinç, B; Oztürk, S; Ozel, S; Cefle, K; Palanduz, S; Tanyeri, H</p>
<p>2009-10-01</p>
<p>The purpose of this study was to determine the genetic instability of peripheral blood lymphocytes from patients diagnosed with oral lichen planus (OLP) by investigation of frequencies of micronuclei (MN) and sister chromatid exchange (SCE). A total of 22 newly diagnosed and untreated patients with OLP of same severity scores and twenty healthy controls participated in this study. They were all non-smokers with no previous history or family history of cancer. The periodontal status, flow rate and buffering capacity of whole mouth saliva were recorded. SCE and MN analyses were performed on peripheral blood lymphocytes of OLP patients and healthy controls. The frequencies of MN (50.00 +/- 22.36) and SCE (6.89 +/- 1.48) in OLP patients were found to be significantly elevated compared with that in normal individuals (25.20 +/- 9.52 and 5.93 +/- 1.31; z = 3.946, P = 0.0001; z = 2.346, P = 0.019). There were no significant differences in the MN frequency and SCE between the two subgroups with reticular or erosive types of OLP. These pilot data indicate an increased genomic instability in peripheral blood lymphocytes of a cohort of Turkish patients diagnosed with oral lichen planus as compared with that of healthy individuals. As patients with OLP may have an increased or potential risk for oral malignancy, these assays could be used in translational research to monitor beneficial effects of interventions and long-term prognosis.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19465021','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19465021"><span>A nucleolar protein RRS1 contributes to chromosome congression.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Gambe, Arni E; Matsunaga, Sachihiro; Takata, Hideaki; Ono-Maniwa, Rika; Baba, Akiko; Uchiyama, Susumu; Fukui, Kiichi</p>
<p>2009-06-18</p>
<p>We report here the functional analysis of human Regulator of Ribosome Synthesis 1 (RRS1) protein during mitosis. We demonstrate that RRS1 localizes in the nucleolus during interphase and is distributed at the chromosome periphery during mitosis. RNA interference experiments revealed that RRS1-depleted cells show abnormalities in chromosome alignment and spindle organization, which result in mitotic delay. RRS1 knockdown also perturbs the centromeric localization of Shugoshin 1 and results in premature separation of sister chromatids. Our results suggest that a nucleolar protein RRS1 contributes to chromosome congression.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/7772731','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/7772731"><span>High frequency of telomeric association in a family with multiple congenital neoplasia.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Dhaliwal, M K; Satya-Prakash, K L; Davis, P C; Pathak, S</p>
<p>1994-01-01</p>
<p>Chromosomal analysis of the peripheral blood cultures of a married couple whose second pregnancy gave birth to twin daughters with multiple congenital malignancies revealed normal karyotypes of 46,XX and 46,XY, respectively. However, in the father's blood, 23.3% of metaphases showed telomere-telomere associations involving single-single and double-double chromatids. Such associations were not observed in the metaphases of the mother. We speculate from these observations that the father's genotype may somehow be responsible for the congenital malignancies in their twin daughters.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=335818','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=335818"><span>ALTERATION OF GENE CONVERSION PATTERNS IN Sordaria fimicola BY SUPPLEMENTATION WITH DNA BASES*</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Kitani, Y.; Olive, Lindsay S.</p>
<p>1970-01-01</p>
<p>Supplementation with DNA bases in crosses of Sordaria fimicola heterozygous for spore color markers (g1, h2) within the gray-spore (g) locus has been found to cause significant alterations in patterns of gene conversion at the two mutant sites. Each base had its own characteristic effect in altering the conversion pattern, and responses of the two mutant sites to the four bases were different in several ways. Also, the responses of the two involved chromatids of the meiotic bivalent were different. PMID:5273454</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/5273454','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/5273454"><span>Alteration of gene conversion patterns in Sordaria fimicola by supplementation with DNA bases.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Kitani, Y; Olive, L S</p>
<p>1970-08-01</p>
<p>Supplementation with DNA bases in crosses of Sordaria fimicola heterozygous for spore color markers (g(1), h(2)) within the gray-spore (g) locus has been found to cause significant alterations in patterns of gene conversion at the two mutant sites. Each base had its own characteristic effect in altering the conversion pattern, and responses of the two mutant sites to the four bases were different in several ways. Also, the responses of the two involved chromatids of the meiotic bivalent were different.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/10593079','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/10593079"><span>First-generation physical map of the Culicoides variipennis (Diptera: Ceratopogonidae) genome.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Nunamaker, R A; Brown, S E; McHolland, L E; Tabachnick, W J; Knudson, D L</p>
<p>1999-11-01</p>
<p>Recombinant cosmids labeled with biotin-11-dUTP or digoxigenin by nick translation were used as in situ hybridization probes to metaphase chromosomes of Culicoides variipennis (Coquillett). Paired fluorescent signals were detected on each arm of sister chromatids and were ordered along the 3 chromosomes. Thirty-three unique probes were mapped to the 3 chromosomes of C. variipennis (2n = 6): 7 to chromosome 1, 20 to chromosome 2, and 6 to chromosome 3. This work represents the first stage in generating a physical map of the genome of C. variipennis.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/7138370-analysis-mutagenic-activity-biohazardous-organics-kanawha-river-sediments-technical-completion-report','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/7138370-analysis-mutagenic-activity-biohazardous-organics-kanawha-river-sediments-technical-completion-report"><span>Analysis of mutagenic activity of biohazardous organics in Kanawha River sediments. Technical completion report</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>White, A.R.; Waldron, M.C.</p>
<p>1988-01-01</p>
<p>Residual chemical contamination of Kanawha River sediments may constitute a health hazard. Sediment cores have been analyzed using a coupled bioassay/chemical fractionation procedure. Both bacterial mutagenicity and sister chromatid exchange (SCE) analyses were conducted on sediment samples. Pocatalico River sediments extracts showed no response in either bacterial mutagenicity assay or SCE assay. Extracts from Armour Creek and the Kanawha River induced mutagenicities in the presence of S9 enzymes. The same extracts produced a significant increase in human chromosomal cross-over events.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24028793','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24028793"><span>BAIT: Organizing genomes and mapping rearrangements in single cells.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Hills, Mark; O'Neill, Kieran; Falconer, Ester; Brinkman, Ryan; Lansdorp, Peter M</p>
<p>2013-01-01</p>
<p>Strand-seq is a single-cell sequencing technique to finely map sister chromatid exchanges (SCEs) and other rearrangements. To analyze these data, we introduce BAIT, software which assigns templates and identifies and localizes SCEs. We demonstrate BAIT can refine completed reference assemblies, identifying approximately 21 Mb of incorrectly oriented fragments and placing over half (2.6 Mb) of the orphan fragments in mm10/GRCm38. BAIT also stratifies scaffold-stage assemblies, potentially accelerating the assembling and finishing of reference genomes. BAIT is available at http://sourceforge.net/projects/bait/.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('http://www.dtic.mil/docs/citations/ADA444255','DTIC-ST'); return false;" href="http://www.dtic.mil/docs/citations/ADA444255"><span>Linking Sister Chromatid Cohesion to Apoptosis and Aneuploidy in the Development of Breast Cancer</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.dtic.mil/">DTIC Science & Technology</a></p>
<p></p>
<p>2005-07-01</p>
<p>antibody. Jurkat cells were ZE in wheat germ extract was .4 Claved fd21 transfected with blank vectors (B), treated with • • incubated in the presence...nonisotopic) hRad21 in wheat germ extracts by FPLC fractions 13-20. Samples were analyzed on an SDS-6% PAGE gel followed by Western bloting with hRda2l C...in vitro translated unlabelled hRad21 in wheat germ extracts and assaying the cleavage in Rad21 immunoblots (Fig. 5C). The broad-spectrum caspase</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17991992','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17991992"><span>Centromere separation and association in the nuclei of an interspecific hybrid between Torenia fournieri and T. baillonii (Scrophulariaceae) during mitosis and meiosis.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Kikuchi, Shinji; Tanaka, Hiroyuki; Wako, Toshiyuki; Tsujimoto, Hisashi</p>
<p>2007-10-01</p>
<p>In the nuclei of some interspecific hybrid and allopolyploid plant species, each genome occupies a separate spatial domain. To analyze this phenomenon, we studied localization of the centromeres in the nuclei of a hybrid between Torenia fournieri and T. baillonii during mitosis and meiosis using three-dimensional fluorescence in situ hybridization (3D-FISH) probed with species-specific centromere repeats. Centromeres of each genome were located separately in undifferentiated cells but not differentiated cells, suggesting that cell division might be the possible force causing centromere separation. However, no remarkable difference of dividing distance was detected between chromatids with different centromeres in anaphase and telophase, indicating that tension of the spindle fiber attached to each chromatid is not the cause of centromere separation in Torenia. In differentiated cells, centromeres in both genomes were not often observed for the expected chromosome number, indicating centromere association. In addition, association of centromeres from the same genome was observed at a higher frequency than between different genomes. This finding suggests that centromeres within one genome are spatially separated from those within the other. This close position may increase possibility of association between centromeres of the same genome. In meiotic prophase, all centromeres irrespective of the genome were associated in a certain portion of the nucleus. Since centromere association in the interspecific hybrid and amphiploid was tighter than that in the diploid parents, it is possible that this phenomenon may be involved in sorting and pairing of homologous chromosomes.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4063914','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4063914"><span>Pseudosynapsis and Decreased Stringency of Meiotic Repair Pathway Choice on the Hemizygous Sex Chromosome of Caenorhabditis elegans Males</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Checchi, Paula M.; Lawrence, Katherine S.; Van, Mike V.; Larson, Braden J.; Engebrecht, JoAnne</p>
<p>2014-01-01</p>
<p>During meiosis, accurate chromosome segregation relies on homology to mediate chromosome pairing, synapsis, and crossover recombination. Crossovers are dependent upon formation and repair of double-strand breaks (DSBs) by homologous recombination (HR). In males of many species, sex chromosomes are largely hemizygous, yet DSBs are induced along nonhomologous regions. Here we analyzed the genetic requirements for meiotic DSB repair on the completely hemizygous X chromosome of Caenorhabditis elegans males. Our data reveal that the kinetics of DSB formation, chromosome pairing, and synapsis are tightly linked in the male germ line. Moreover, DSB induction on the X is concomitant with a brief period of pseudosynapsis that may allow X sister chromatids to masquerade as homologs. Consistent with this, neither meiotic kleisins nor the SMC-5/6 complex are essential for DSB repair on the X. Furthermore, early processing of X DSBs is dependent on the CtIP/Sae2 homolog COM-1, suggesting that as with paired chromosomes, HR is the preferred pathway. In contrast, the X chromosome is refractory to feedback mechanisms that ensure crossover formation on autosomes. Surprisingly, neither RAD-54 nor BRC-2 are essential for DSB repair on the X, suggesting that unlike autosomes, the X is competent for repair in the absence of HR. When both RAD-54 and the structure-specific nuclease XPF-1 are abrogated, X DSBs persist, suggesting that single-strand annealing is engaged in the absence of HR. Our findings indicate that alteration in sister chromatid interactions and flexibility in DSB repair pathway choice accommodate hemizygosity on sex chromosomes. PMID:24939994</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5733479','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5733479"><span>Multiple Duties for Spindle Assembly Checkpoint Kinases in Meiosis</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Marston, Adele L.; Wassmann, Katja</p>
<p>2017-01-01</p>
<p>Cell division in mitosis and meiosis is governed by evolutionary highly conserved protein kinases and phosphatases, controlling the timely execution of key events such as nuclear envelope breakdown, spindle assembly, chromosome attachment to the spindle and chromosome segregation, and cell cycle exit. In mitosis, the spindle assembly checkpoint (SAC) controls the proper attachment to and alignment of chromosomes on the spindle. The SAC detects errors and induces a cell cycle arrest in metaphase, preventing chromatid separation. Once all chromosomes are properly attached, the SAC-dependent arrest is relieved and chromatids separate evenly into daughter cells. The signaling cascade leading to checkpoint arrest depends on several protein kinases that are conserved from yeast to man. In meiosis, haploid cells containing new genetic combinations are generated from a diploid cell through two specialized cell divisions. Though apparently less robust, SAC control also exists in meiosis. Recently, it has emerged that SAC kinases have additional roles in executing accurate chromosome segregation during the meiotic divisions. Here, we summarize the main differences between mitotic and meiotic cell divisions, and explain why meiotic divisions pose special challenges for correct chromosome segregation. The less-known meiotic roles of the SAC kinases are described, with a focus on two model systems: yeast and mouse oocytes. The meiotic roles of the canonical checkpoint kinases Bub1, Mps1, the pseudokinase BubR1 (Mad3), and Aurora B and C (Ipl1) will be discussed. Insights into the molecular signaling pathways that bring about the special chromosome segregation pattern during meiosis will help us understand why human oocytes are so frequently aneuploid. PMID:29322045</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21768208','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21768208"><span>Evaluation of differential representative values between Chinese hamster cells and human lymphocytes in mitomycin C-induced cytogenetic assays and caspase-3 activity.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Liao, Pei-Hu; Lin, Ruey-Hseng; Yang, Ming-Ling; Li, Yi-Ching; Kuan, Yu-Hsiang</p>
<p>2012-03-01</p>
<p>Chinese hamster ovary (CHO) cells, its lung fibroblasts (V79), and human lymphocytes are routinely used in in vitro cytogenetic assays, which include micronuclei (MN), sister chromatid exchange (SCE), and chromosome aberration (CA) assays. Mitomycin C (MMC), a DNA cross-link alkylating agent, is both an anticancer medicine and a carcinogen. To study the differential representative values of cell types in MMC-treated cytogenetic assays and its upstream factor, cysteine aspartic acid-specific protease (caspase)-3. Among the chosen cell types, lymphocytes expressed the highest sensitivity in all three MMC-induced assays, whereas CHO and V79 showed varied sensitivity in different assays. In MN assay, the sensitivity of CHO is higher than or equal to V79; in SCE assay, the sensitivity of CHO is the same as V79; and in CA assay, the sensitivity of CHO is higher than V79. In-depth analysis of CA revealed that in chromatid breaks and dicentrics formation, lymphocyte was the most sensitive of all and CHO was more sensitive than V79; and in acentrics and interchanges formation, lymphocyte was much more sensitive than the others. Furthermore, we found caspase-3 activity plays an important role in MMC-induced cytogenetic assays, with MMC-induced caspase-3 activity resulting in more sensitivity in lymphocytes than in CHO and V79. Based on these findings, lymphocyte will make a suitable predictive or representative control reference in cytogenetic assays and caspase-3 activity with its high specificity, positive predictive value, and sensitivity.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/7527908','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/7527908"><span>Analysis of chromosomal aberrations, sister-chromatid exchanges and micronuclei in peripheral lymphocytes of pharmacists before and after working with cytostatic drugs.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Roth, S; Norppa, H; Järventaus, H; Kyyrönen, P; Ahonen, M; Lehtomäki, J; Sainio, H; Sorsa, M</p>
<p>1994-12-01</p>
<p>The frequencies of chromosome aberrations, SCEs and micronuclei (cytokinesis-block method) in blood lymphocytes were compared among six nonsmoking female pharmacists before and after 1 year of working with cytostatic drugs. All possible precautions were taken to avoid exposure to cytostatics, including proper protective clothing and a monitored, negative-pressured working environment with vertical laminar flow cabinet. As referents, an age-matched group of six nonsmoking female hospital workers not dealing with cytostatics was simultaneously sampled twice with the same time interval. The pharmacists showed a marginally higher mean frequency of SCEs/cell (6.3; P = 0.049) after the working period than 1 year earlier (5.8). On the other hand, the referents, with no obvious exposure, had a higher mean number of cells with chromatid-type aberrations, gaps excluded, in the second sampling (2.0%; P = 0.048) than in the first one (0.5%). In addition, a slight (P = 0.055) trend towards a higher frequency of micronucleated binucleate cells was observed in the second sampling for both the exposed and control subjects. As such findings suggest technical variation in the cytogenetic parameters, the small difference observed in SCEs for the pharmacists between the two samplings was probably not related to the cytostatics exposure. No statistically significant differences were observed for any of the cytogenetic parameters in comparisons between the pharmacists and the referents. The findings suggest that caution should be exercised in comparing results obtained from two different samplings in prospective cytogenetic studies.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26157718','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26157718"><span>A study of professional radiation hazards in CT scan and nuclear medicine workers using GTG-banding and solid stain.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Changizi, Vahid; Alizadeh, Mohammad Hossein; Mousavi, Akbar</p>
<p>2015-01-01</p>
<p>CT scan and nuclear medicine exams deliver a great part of medical exposures. This study examined professional radiation hazards in CT scan and nuclear medicine workers. In a cross sectional study 30 occupationally exposed workers and 7 controls (all from personnel of a laboratory) were selected. Physical dosimetry was performed for exposed workers. Blood samples were obtained from the experimental and control groups. Three culture mediums for each one were prepared in due to routine chromosome analysis using G-banding and solid stain. There were significant increased incidence of chromatid gap (ctg) and chromatid break (ctb) with mean±SD frequencies of 3±0.84 and 3.1±1.40 per 100 cells respectively in the nuclear medicine workers versus controls with mean±SD frequencies of 1.9±0.69 and 1.3±0.84 for ctg and ctb, respectively. Chromosome gaps (chrg) were higher significantly in the nuclear medicine population (2.47±0.91) than in controls (1.4±0.9) (p< 0.05). In CT scan group the ctg and ctb were increased with a mean±SD frequency of 2.7±0.79 and 2.6±0.91 per 100 cells respectively compared with control group. The mean±SD frequencies of the chrb were 2.0±0.75 and 0.86±0.690 per 100 cells for exposed workers and control group, respectively. This study showed chromosome aberrations in peripheral lymphocytes using solid stain method are reasonable biomarker reflecting personnel radiation damage.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26615478','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26615478"><span>Effect of SPL (Spent Pot Liner) and its main components on root growth, mitotic activity and phosphorylation of Histone H3 in Lactuca sativa L.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Freitas, Aline Silva; Fontes Cunha, Isabela Martinez; Andrade-Vieira, Larissa Fonseca; Techio, Vânia Helena</p>
<p>2016-02-01</p>
<p>Spent Pot Liner (SPL) is a solid waste from the aluminum industry frequently disposed of in industrial landfills; it can be leached and contaminate the soil, sources of drinking water and plantations, and thus may pose a risk to human health and to ecosystems. Its composition is high variable, including cyanide, fluoride and aluminum salts, which are highly toxic and environmental pollutants. This study evaluated the effect of SPL and its main components on root growth and the mitosis of Lactuca sativa, by investigating the mechanisms of cellular and chromosomal alterations with the aid of immunolocalization. To this end, newly emerged roots of L. sativa were exposed to SPL and its main components (solutions of cyanide, fluoride and aluminum) and to calcium chloride (control) for 48h. After this, root length was measured and cell cycle was examined by means of conventional cytogenetics and immunolocalization. Root growth was inhibited in the treatments with SPL and aluminum; chromosomal and nuclear alterations were observed in all treatments. The immunolocalization evidenced normal dividing cells with regular temporal and spatial distribution of histone H3 phosphorylation at serine 10 (H3S10ph). However, SPL and its main components inhibited the phosphorylation of histone H3 at serine 10, inactivated pericentromeric regions and affected the cohesion of sister chromatids, thus affecting the arrangement of chromosomes in the metaphase plate and separation of chromatids in anaphase. In addition, these substances induced breaks in pericentromeric regions, characterized as fragile sites. Copyright © 2015 Elsevier Inc. All rights reserved.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3903996','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3903996"><span>Sufficient Amounts of Functional HOP2/MND1 Complex Promote Interhomolog DNA Repair but Are Dispensable for Intersister DNA Repair during Meiosis in Arabidopsis[W</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Uanschou, Clemens; Ronceret, Arnaud; Von Harder, Mona; De Muyt, Arnaud; Vezon, Daniel; Pereira, Lucie; Chelysheva, Liudmila; Kobayashi, Wataru; Kurumizaka, Hitoshi; Schlögelhofer, Peter; Grelon, Mathilde</p>
<p>2013-01-01</p>
<p>During meiosis, homologous recombination (HR) is essential to repair programmed DNA double-strand breaks (DSBs), and a dedicated protein machinery ensures that the homologous chromosome is favored over the nearby sister chromatid as a repair template. The HOMOLOGOUS-PAIRING PROTEIN2/MEIOTIC NUCLEAR DIVISION PROTEIN1 (HOP2/MND1) protein complex has been identified as a crucial factor of meiotic HR in Arabidopsis thaliana, since loss of either MND1 or HOP2 results in failure of DNA repair. We isolated two mutant alleles of HOP2 (hop2-2 and hop2-3) that retained the capacity to repair meiotic DSBs via the sister chromatid but failed to use the homologous chromosome. We show that in these alleles, the recombinases RADIATION SENSITIVE51 (RAD51) and DISRUPTED MEIOTIC cDNA1 (DMC1) are loaded, but only the intersister DNA repair pathway is activated. The hop2-2 phenotype is correlated with a decrease in HOP2/MND1 complex abundance. In hop2-3, a truncated HOP2 protein is produced that retains its ability to bind to DMC1 and DNA but forms less stable complexes with MND1 and fails to efficiently stimulate DMC1-driven D-loop formation. Genetic analyses demonstrated that in the absence of DMC1, HOP2/MND1 is dispensable for RAD51-mediated intersister DNA repair, while in the presence of DMC1, a minimal amount of functional HOP2/MND1 is essential to drive intersister DNA repair. PMID:24363313</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('http://www.dtic.mil/docs/citations/ADA184570','DTIC-ST'); return false;" href="http://www.dtic.mil/docs/citations/ADA184570"><span>Field Verification Program (Aquatic Disposal). Sister Chromatid Exchange in Marine Polychaetes Exposed to Black Rock Harbor Sediment.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.dtic.mil/">DTIC Science & Technology</a></p>
<p></p>
<p>1985-07-01</p>
<p>the reservoi r Iones and were connected t - to (-. m capacit t itted wit ’ el on diaphragms. These pumps 4, . fI Stir ear Sigure . i-pended se(ti ret’t...phases served as the control. Each treatment had 15 worms. The worms were fed prawn flakes (ADT-Prime, Aquatic Diet Technology, Brooklyn, N. Y .) in a...counter - -- 4 relay o switch solenoid valve -- ani; seawater mnf~ water wtr trap "- lo -t chamber,t a I mix"n chamber float switch distribution *chamber</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/8249156','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/8249156"><span>[The clinical and cytogenetic characteristics of the children born to persons with a history of 1st- and 2d-degree acute radiation sickness as a result of the accident at the Chernobyl Atomic Electric Power Station].</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Stepanova, E I; Vaniurikhina, E A</p>
<p>1993-01-01</p>
<p>We have examined 15 children (born in 1987-1988), whose fathers liquidated the aftereffects of the accident at Chernobyl Nuclear Power Plant and suffered from acute radiation sickness of the 1st and 2nd stages and 50 children of the control group. The obtained data showed that the number of small developmental abnormalities (stigmas of dysembryogenesis) increased as well as the chromatid aberration frequency as compared with the control group.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19782954','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19782954"><span>An overview of plant centromeres.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Wang, Guixiang; Zhang, Xueyong; Jin, Weiwei</p>
<p>2009-09-01</p>
<p>The centromere is a defining region that mediates chromosome attachment to kinetochore microtubules and proper segregation of the sister chromatids. Intriguingly, satellite DNA and centromeric retrotransposon as major DNA constituents of centromere showed baffling diversification and species-specific. However, the key kinetochore proteins are conserved in both plants and animals, particularly the centromere-specific histone H3-like protein (CENH3) in all functional centromeres. Recent studies have highlighted the importance of epigenetic mechanisms in the establishment and maintenance of centromere identity. Here, we review the progress and compendium of research on plant centromere in the light of recent data.</p>
</li>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19253750','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19253750"><span>Cytotoxic effects of pesticides in somatic cells of Vicia faba L.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Pandey, R M</p>
<p>2008-01-01</p>
<p>The effects of pesticides (Endosulfan, Dieldrin, Aldrin) on cell division and chromosomal morphology of Vicia faba L. were studied. The results showed that the pesticides are mitode-pressive in higher concentrations and mitopromotor in lower concentrations and induced a variety of chromosomal abnormalities such as stickiness, fragments, chromatid separation, disturbed metaphase, C-mitosis, laggards, precocious movement and late separation where lagging chromosomes were predominant. The concentration of 500 ppm or above, for all the pesticides used in the present study showed pronounced toxic effect. In remaining treatments, although the milotic index was improved but less than that of absolute controls.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/12929726','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/12929726"><span>The usefulness of cytogenetic parameters, level of p53 protein and endogenous glutathione as intermediate end-points in raw betel-nut genotoxicity.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Kumpawat, K; Chatterjee, A</p>
<p>2003-07-01</p>
<p>Betel-nut (BN) chewing related oral mucosal lesions are potential hazards to a large population worldwide. Genotoxicity of betel alkaloids, polyphenol and tannin fractions have been reported. It has been shown earlier that BN ingredients altered the level of endogenous glutathione (GSH) which could modulate the host susceptibility to the action of other chemical carcinogens. The north-east Indian variety of BN, locally known as 'kwai', is raw, wet and consumed unprocessed with betel-leaf and slaked lime and contains higher alkaloids, polyphenol and tannins as compared to the dried one. Therefore, the purpose of this study was to investigate the extent of DNA damage, pattern of cell kinetics, the level of p53-protein and endogenous GSH in kwai chewers in the tribal population of Meghalaya state in the northeastern region of India with an aim to see whether these end-points could serve as biomarkers of genetic damage of relevance for genotoxic/carcinogenic process. The present data show higher DNA damage, delay in cell kinetics, p53 expression and lower GSH-level in heavy chewers (HC) than nonchewers (NC). The influence of bleomycin (BLM) on chromatid break induction in G2-phase of peripheral blood lymphocytes in NC and HC has been analysed to determine individual susceptibility to carcinogenic assaults. HC showed higher induction of chromatid breaks than NC. Risk assessment in this study suggests an interaction between carcinogen exposure and mutagen sensitivity measures, risk estimates being higher in those individuals who both consume kwai and express sensitivity to free radical oxygen damage in vitro. From this study it seems that besides cytogenetical parameters, the level of endogenous GSH and the level of p53 protein could act as effective biomarkers for kwai chewers.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19383157','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19383157"><span>Meiosis genes in Daphnia pulex and the role of parthenogenesis in genome evolution.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Schurko, Andrew M; Logsdon, John M; Eads, Brian D</p>
<p>2009-04-21</p>
<p>Thousands of parthenogenetic animal species have been described and cytogenetic manifestations of this reproductive mode are well known. However, little is understood about the molecular determinants of parthenogenesis. The Daphnia pulex genome must contain the molecular machinery for different reproductive modes: sexual (both male and female meiosis) and parthenogenetic (which is either cyclical or obligate). This feature makes D. pulex an ideal model to investigate the genetic basis of parthenogenesis and its consequences for gene and genome evolution. Here we describe the inventory of meiotic genes and their expression patterns during meiotic and parthenogenetic reproduction to help address whether parthenogenesis uses existing meiotic and mitotic machinery, or whether novel processes may be involved. We report an inventory of 130 homologs representing over 40 genes encoding proteins with diverse roles in meiotic processes in the genome of D. pulex. Many genes involved in cell cycle regulation and sister chromatid cohesion are characterized by expansions in copy number. In contrast, most genes involved in DNA replication and homologous recombination are present as single copies. Notably, RECQ2 (which suppresses homologous recombination) is present in multiple copies while DMC1 is the only gene in our inventory that is absent in the Daphnia genome. Expression patterns for 44 gene copies were similar during meiosis versus parthenogenesis, although several genes displayed marked differences in expression level in germline and somatic tissues. We propose that expansions in meiotic gene families in D. pulex may be associated with parthenogenesis. Taking into account our findings, we provide a mechanistic model of parthenogenesis, highlighting steps that must differ from meiosis including sister chromatid cohesion and kinetochore attachment.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2680839','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2680839"><span>Meiosis genes in Daphnia pulex and the role of parthenogenesis in genome evolution</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Schurko, Andrew M; Logsdon, John M; Eads, Brian D</p>
<p>2009-01-01</p>
<p>Background Thousands of parthenogenetic animal species have been described and cytogenetic manifestations of this reproductive mode are well known. However, little is understood about the molecular determinants of parthenogenesis. The Daphnia pulex genome must contain the molecular machinery for different reproductive modes: sexual (both male and female meiosis) and parthenogenetic (which is either cyclical or obligate). This feature makes D. pulex an ideal model to investigate the genetic basis of parthenogenesis and its consequences for gene and genome evolution. Here we describe the inventory of meiotic genes and their expression patterns during meiotic and parthenogenetic reproduction to help address whether parthenogenesis uses existing meiotic and mitotic machinery, or whether novel processes may be involved. Results We report an inventory of 130 homologs representing over 40 genes encoding proteins with diverse roles in meiotic processes in the genome of D. pulex. Many genes involved in cell cycle regulation and sister chromatid cohesion are characterized by expansions in copy number. In contrast, most genes involved in DNA replication and homologous recombination are present as single copies. Notably, RECQ2 (which suppresses homologous recombination) is present in multiple copies while DMC1 is the only gene in our inventory that is absent in the Daphnia genome. Expression patterns for 44 gene copies were similar during meiosis versus parthenogenesis, although several genes displayed marked differences in expression level in germline and somatic tissues. Conclusion We propose that expansions in meiotic gene families in D. pulex may be associated with parthenogenesis. Taking into account our findings, we provide a mechanistic model of parthenogenesis, highlighting steps that must differ from meiosis including sister chromatid cohesion and kinetochore attachment. PMID:19383157</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23528318','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23528318"><span>Nitric oxide coordinates development of genomic instability in realization of combined effect with ionizing radiation.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Mikhailenko, V M; Diomina, E A; Muzalov, I I; Gerashchenko, B I</p>
<p>2013-03-01</p>
<p>The aim of this study was to investigate the ability of environmental nitrogen oxides or natural nitric oxide (NO) donors to modify free radicals ba-lance and development of genomic instability alone or in combination with ionizing radiation. Genotoxicity and cytogenetic abnormalities were assessed in vitro in peripheral blood lymphocytes (PBL) isolated from healthy humans or in vivo in rats PBL. Human PBL were treated with physiologically relevant NO donor - S-Nitrosoglutathione and X-ray irradiation. The inhalation treatment of animals with NO was carried out in chamber with purified gaseous NO mixed inside with air. Levels of S-Nitrosohemoglobin and methemoglobin in the blood were assessed with electron paramagnetic resonance. The total level of reactive oxygen and nitrogen species in PBL was determined fluorometrically, and serum levels of reactive oxygen species was determined by spectrophotometric assay. DNA damages were assessed by alkaline single-cell gel electrophoresis. The frequency of chromosomal aberrations in human PBL measured with the conventional cytogenetic assay in metaphase cells on short-term (52 h) and long-term (72 h) cultures. Environmental nitrogen oxides or release of NO from stable complexes with biomolecules (such as S-Nitrosothiols) intensified generation of free radicals, DNA damage and development of genomic instability alone or in combination with ionizing radiation. Treatment of PBL by S-Nitrosoglutathione caused prevalent induction of chromatid type but irradiation - chromosome aberrations. The dose dependence of chromatid-type aberrations observed in human PBL after combined influence of S-Nitrosoglutathione and ionizing radiation indicates a crucial role of NO in the formation of chromosomal instability. NO can deregulate free radicals balance resulted in genotoxic effect, posttranslational modification of repair enzymes and thus coordinated development of genomic instability and increase of cancer risk.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4041464','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4041464"><span>Requirement for Parp-1 and DNA ligases 1 or 3 but not of Xrcc1 in chromosomal translocation formation by backup end joining</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Soni, Aashish; Siemann, Maria; Grabos, Martha; Murmann, Tamara; Pantelias, Gabriel E.; Iliakis, George</p>
<p>2014-01-01</p>
<p>In mammalian cells, ionizing radiation (IR)-induced DNA double-strand breaks (DSBs) are repaired in all phases of the cell cycle predominantly by classical, DNA-PK-dependent nonhomologous end joining (D-NHEJ). Homologous recombination repair (HRR) is functional during the S- and G2-phases, when a sister chromatid becomes available. An error-prone, alternative form of end joining, operating as backup (B-NHEJ) functions robustly throughout the cell cycle and particularly in the G2-phase and is thought to backup predominantly D-NHEJ. Parp-1, DNA-ligases 1 (Lig1) and 3 (Lig3), and Xrcc1 are implicated in B-NHEJ. Chromosome and chromatid translocations are manifestations of erroneous DSB repair and are crucial culprits in malignant transformation and IR-induced cell lethality. We analyzed shifts in translocation formation deriving from defects in D-NHEJ or HRR in cells irradiated in the G2-phase and identify B-NHEJ as the main DSB repair pathway backing up both of these defects at the cost of a large increase in translocation formation. Our results identify Parp-1 and Lig1 and 3 as factors involved in translocation formation and show that Xrcc1 reinforces the function of Lig3 in the process without being required for it. Finally, we demonstrate intriguing connections between B-NHEJ and DNA end resection in translocation formation and show that, as for D-NHEJ and HRR, the function of B-NHEJ facilitates the recovery from the G2-checkpoint. These observations advance our understanding of chromosome aberration formation and have implications for the mechanism of action of Parp inhibitors. PMID:24748665</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24748665','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24748665"><span>Requirement for Parp-1 and DNA ligases 1 or 3 but not of Xrcc1 in chromosomal translocation formation by backup end joining.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Soni, Aashish; Siemann, Maria; Grabos, Martha; Murmann, Tamara; Pantelias, Gabriel E; Iliakis, George</p>
<p>2014-06-01</p>
<p>In mammalian cells, ionizing radiation (IR)-induced DNA double-strand breaks (DSBs) are repaired in all phases of the cell cycle predominantly by classical, DNA-PK-dependent nonhomologous end joining (D-NHEJ). Homologous recombination repair (HRR) is functional during the S- and G2-phases, when a sister chromatid becomes available. An error-prone, alternative form of end joining, operating as backup (B-NHEJ) functions robustly throughout the cell cycle and particularly in the G2-phase and is thought to backup predominantly D-NHEJ. Parp-1, DNA-ligases 1 (Lig1) and 3 (Lig3), and Xrcc1 are implicated in B-NHEJ. Chromosome and chromatid translocations are manifestations of erroneous DSB repair and are crucial culprits in malignant transformation and IR-induced cell lethality. We analyzed shifts in translocation formation deriving from defects in D-NHEJ or HRR in cells irradiated in the G2-phase and identify B-NHEJ as the main DSB repair pathway backing up both of these defects at the cost of a large increase in translocation formation. Our results identify Parp-1 and Lig1 and 3 as factors involved in translocation formation and show that Xrcc1 reinforces the function of Lig3 in the process without being required for it. Finally, we demonstrate intriguing connections between B-NHEJ and DNA end resection in translocation formation and show that, as for D-NHEJ and HRR, the function of B-NHEJ facilitates the recovery from the G2-checkpoint. These observations advance our understanding of chromosome aberration formation and have implications for the mechanism of action of Parp inhibitors. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26591571','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26591571"><span>[THE INFLUENCE OF THE PREPARATION PRETREATMENT ON IN SITU DETECTION OF 5-METHYLCYTOSINE IN METAPHASE CHROMOSOMES AND IN INTERPHASE NUCLEI].</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Grudinina, N A; Sasina, L K; Noniashvili, E M; Neronova, E G; Pavlinova, L I; Suchkova, I O; Sofronov, G A; Patkin, E L</p>
<p>2015-01-01</p>
<p>Qualitative and quantitate analysis of DNA methylation in situ at the level of cells, chromosomes and chromosomal domains is extremely important for the diagnosis and treatment of various diseases, the study of ageing and the consequences of environmental impacts. An important question arises, whether the revealed in situ methylation pattern reflects DNA methylation per se and (or) availability of the DNA for antibodies, which in turn depends on the peculiarities of chromatin structure and chromosome condensation. These events can lead to an incorrect evaluation of the actual pattern of DNA methylation. To avoid this shortcoming as far as possible, we have modified the most widely used method of revealing 5-methylcytosine in situ with monoclonal antibodies. Here we have shown that the detection of DNA methylation staining of chromosomes including C-heterochromatin, chromosomal arms and sister chromatids is drastically dependent on pretreatment of chromosomal preparations for immunocytochemical study using fluorescent antibodies. Using undifferentiated stem cells of mouse embryonal carcinoma line F9, it has been found that change in preparations storage results in a sharp fluorescence decrease up to complete disappearance of the signal in centromeric heterochromatin. With the help of the method described in the work, we have first revealed the asymmetry of sister chromatids methylation in metaphase chromosomes of F9 cell and lymphocytes of human periphery blood. This may lead to asymmetry of transcriptional signature of daughter cells after division. The proposed here modification of 5-methylcytosine detection in situ provides a more complete characterization of methylation of chromosomes and chromosomal domains, compared to previously published methods.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29378067','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29378067"><span>Associations of polymorphisms in the cytokine genes IL1β (rs16944), IL6 (rs1800795), IL12b (rs3212227) and growth factor VEGFA (rs2010963) with anthracosilicosis in coal miners in Russia and related genotoxic effects.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Volobaev, Valentin P; Larionov, Aleksey V; Kalyuzhnaya, Ekaterina E; Serdyukova, Ekaterina S; Yakovleva, Svetlana; Druzhinin, Vladimir G; Babich, Olga O; Hill, Elena G; Semenihin, Victor A; Panev, Nikolay I; Minina, Varvara I; Sivanesan, Saravana Devi; Naoghare, Pravin; da Silva, Juliana; Barcelos, Gustavo R M; Prosekov, Alexander Y</p>
<p>2018-04-13</p>
<p>Anthracosilicosis (AS), a prevalent form of pneumoconiosis among coal miners, results from the accumulation of carbon and silica in the lungs from inhaled coal dust. This study investigated genotoxic effects and certain cytokine genes polymorphic variants in Russian coal miners with АS. Peripheral leukocytes were sampled from 129 patients with AS confirmed by X-ray and tissue biopsy and from 164 asymptomatic coal miners. Four single-nucleotide polymorphisms were genotyped in the extracted DNA samples: IL1β T-511C (rs16944), IL6 C-174G (rs1800795), IL12b A1188C (rs3212227) and VEGFA C634G (rs2010963). Genotoxic effects were assessed by the analysis of chromosome aberrations in cultured peripheral lymphocytes. The mean frequency of chromatid-type aberrations and chromosome-type aberrations, namely, chromatid-type breaks and dicentric chromosomes, was found to be higher in AS patients [3.70 (95% confidence interval {CI}, 3.29-4.10) and 0.28 (95% CI, 0.17-0.38)] compared to the control group [2.41 (95% CI, 2.00-2.82) and 0.09 (95% CI, 0.03-0.15)], respectively. IL1β gene T/T genotype (rs16944) was associated with AS [17.83% in AS patients against 4.35% in healthy donors, odds ratio = 4.77 (1.88-12.15), P < 0.01]. A significant increase in the level of certain chromosome interchanges among AS donors is of interest because such effects are typical for radiation damage and caused by acute oxidative stress. IL1β T allele probably may be considered as an AS susceptibility factor among coal miners.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4183305','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4183305"><span>Absence of SUN-domain protein Slp1 blocks karyogamy and switches meiotic recombination and synapsis from homologs to sister chromatids</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Vasnier, Christelle; de Muyt, Arnaud; Zhang, Liangran; Tessé, Sophie; Kleckner, Nancy E.; Zickler, Denise; Espagne, Eric</p>
<p>2014-01-01</p>
<p>Karyogamy, the process of nuclear fusion is required for two haploid gamete nuclei to form a zygote. Also, in haplobiontic organisms, karyogamy is required to produce the diploid nucleus/cell that then enters meiosis. We identify sun like protein 1 (Slp1), member of the mid–Sad1p, UNC-84–domain ubiquitous family, as essential for karyogamy in the filamentous fungus Sordaria macrospora, thus uncovering a new function for this protein family. Slp1 is required at the last step, nuclear fusion, not for earlier events including nuclear movements, recognition, and juxtaposition. Correspondingly, like other family members, Slp1 localizes to the endoplasmic reticulum and also to its extensions comprising the nuclear envelope. Remarkably, despite the absence of nuclear fusion in the slp1 null mutant, meiosis proceeds efficiently in the two haploid “twin” nuclei, by the same program and timing as in diploid nuclei with a single dramatic exception: the normal prophase program of recombination and synapsis between homologous chromosomes, including loading of recombination and synaptonemal complex proteins, occurs instead between sister chromatids. Moreover, the numbers of recombination-initiating double-strand breaks (DSBs) and ensuing recombinational interactions, including foci of the essential crossover factor Homo sapiens enhancer of invasion 10 (Hei10), occur at half the diploid level in each haploid nucleus, implying per-chromosome specification of DSB formation. Further, the distribution of Hei10 foci shows interference like in diploid meiosis. Centromere and spindle dynamics, however, still occur in the diploid mode during the two meiotic divisions. These observations imply that the prophase program senses absence of karyogamy and/or absence of a homolog partner and adjusts the interchromosomal interaction program accordingly. PMID:25210014</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4788232','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4788232"><span>Centromere Locations in Brassica A and C Genomes Revealed Through Half-Tetrad Analysis</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Mason, Annaliese S.; Rousseau-Gueutin, Mathieu; Morice, Jérôme; Bayer, Philipp E.; Besharat, Naghmeh; Cousin, Anouska; Pradhan, Aneeta; Parkin, Isobel A. P.; Chèvre, Anne-Marie; Batley, Jacqueline; Nelson, Matthew N.</p>
<p>2016-01-01</p>
<p>Locating centromeres on genome sequences can be challenging. The high density of repetitive elements in these regions makes sequence assembly problematic, especially when using short-read sequencing technologies. It can also be difficult to distinguish between active and recently extinct centromeres through sequence analysis. An effective solution is to identify genetically active centromeres (functional in meiosis) by half-tetrad analysis. This genetic approach involves detecting heterozygosity along chromosomes in segregating populations derived from gametes (half-tetrads). Unreduced gametes produced by first division restitution mechanisms comprise complete sets of nonsister chromatids. Along these chromatids, heterozygosity is maximal at the centromeres, and homologous recombination events result in homozygosity toward the telomeres. We genotyped populations of half-tetrad-derived individuals (from Brassica interspecific hybrids) using a high-density array of physically anchored SNP markers (Illumina Brassica 60K Infinium array). Mapping the distribution of heterozygosity in these half-tetrad individuals allowed the genetic mapping of all 19 centromeres of the Brassica A and C genomes to the reference Brassica napus genome. Gene and transposable element density across the B. napus genome were also assessed and corresponded well to previously reported genetic map positions. Known centromere-specific sequences were located in the reference genome, but mostly matched unanchored sequences, suggesting that the core centromeric regions may not yet be assembled into the pseudochromosomes of the reference genome. The increasing availability of genetic markers physically anchored to reference genomes greatly simplifies the genetic and physical mapping of centromeres using half-tetrad analysis. We discuss possible applications of this approach, including in species where half-tetrads are currently difficult to isolate. PMID:26614742</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26614742','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26614742"><span>Centromere Locations in Brassica A and C Genomes Revealed Through Half-Tetrad Analysis.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Mason, Annaliese S; Rousseau-Gueutin, Mathieu; Morice, Jérôme; Bayer, Philipp E; Besharat, Naghmeh; Cousin, Anouska; Pradhan, Aneeta; Parkin, Isobel A P; Chèvre, Anne-Marie; Batley, Jacqueline; Nelson, Matthew N</p>
<p>2016-02-01</p>
<p>Locating centromeres on genome sequences can be challenging. The high density of repetitive elements in these regions makes sequence assembly problematic, especially when using short-read sequencing technologies. It can also be difficult to distinguish between active and recently extinct centromeres through sequence analysis. An effective solution is to identify genetically active centromeres (functional in meiosis) by half-tetrad analysis. This genetic approach involves detecting heterozygosity along chromosomes in segregating populations derived from gametes (half-tetrads). Unreduced gametes produced by first division restitution mechanisms comprise complete sets of nonsister chromatids. Along these chromatids, heterozygosity is maximal at the centromeres, and homologous recombination events result in homozygosity toward the telomeres. We genotyped populations of half-tetrad-derived individuals (from Brassica interspecific hybrids) using a high-density array of physically anchored SNP markers (Illumina Brassica 60K Infinium array). Mapping the distribution of heterozygosity in these half-tetrad individuals allowed the genetic mapping of all 19 centromeres of the Brassica A and C genomes to the reference Brassica napus genome. Gene and transposable element density across the B. napus genome were also assessed and corresponded well to previously reported genetic map positions. Known centromere-specific sequences were located in the reference genome, but mostly matched unanchored sequences, suggesting that the core centromeric regions may not yet be assembled into the pseudochromosomes of the reference genome. The increasing availability of genetic markers physically anchored to reference genomes greatly simplifies the genetic and physical mapping of centromeres using half-tetrad analysis. We discuss possible applications of this approach, including in species where half-tetrads are currently difficult to isolate. Copyright © 2016 by the Genetics Society of America.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29410075','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29410075"><span>The small molecule CS1 inhibits mitosis and sister chromatid resolution in HeLa cells.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Wu, Xingkang; Li, Zhenyu; Shen, Yuemao</p>
<p>2018-05-01</p>
<p>Mitosis, the most dramatic event in the cell cycle, involves the reorganization of virtually all cellular components. Antimitotic agents are useful for dissecting the mechanism of this reorganization. Previously, we found that the small molecule CS1 accumulates cells in G2/M phase [1], but the mechanism of its action remains unknown. Cell cycle analysis, live cell imaging and nuclear staining were used. Chromosomal morphology was detected by chromosome spreading. The effects of CS1 on microtubules were confirmed by tubulin polymerization, colchicine tubulin-binding, cellular tubulin polymerization and immunofluorescence assays and by analysis of microtubule dynamics and molecular modeling. Histone phosphoproteomics was performed using mass spectrometry. Cell signaling cascades were analyzed using immunofluorescence, immunoprecipitation, immunoblotting, siRNA knockdown and chemical inhibition of specific proteins. The small molecule CS1 was shown to be an antimitotic agent. CS1 potently inhibited microtubule polymerization via interaction with the colchicine-binding pocket of tubulin in vitro and inhibited the formation of the spindle apparatus by reducing the bulk of growing microtubules in HeLa cells, which led to activation of the spindle assembly checkpoint (SAC) and mitotic arrest of HeLa cells. Compared with colchicine, CS1 impaired the progression of sister chromatid resolution independent of cohesin dissociation, and this was reversed by the removal of CS1. Additionally, CS1 induced unique histone phosphorylation patterns distinct from those induced by colchicine. CS1 is a unique antimitotic small molecule and a powerful tool with unprecedented value over colchicine that makes it possible to specifically and conditionally perturb mitotic progression. Copyright © 2018 Elsevier B.V. All rights reserved.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28108507','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28108507"><span>FLT3 and JAK2 Mutations in Acute Myeloid Leukemia Promote Interchromosomal Homologous Recombination and the Potential for Copy Neutral Loss of Heterozygosity.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Gaymes, Terry J; Mohamedali, Azim; Eiliazadeh, Anthony L; Darling, David; Mufti, Ghulam J</p>
<p>2017-04-01</p>
<p>Acquired copy neutral LOH (CN-LOH) is a frequent occurrence in myeloid malignancies and is often associated with resistance to standard therapeutic modalities and poor survival. Here, we show that constitutive signaling driven by mutated FLT3 and JAK2 confers interchromosomal homologous recombination (iHR), a precedent for CN-LOH. Using a targeted recombination assay, we determined significant iHR activity in internal tandem duplication FLT3 (FLT3-ITD) and JAK2V617F-mutated cells. Sister chromatid exchanges, a surrogate measure of iHR, was significantly elevated in primary FLT3-ITD normal karyotype acute myeloid leukemia (NK-AML) compared with wild-type FLT3 NK-AML. HR was harmonized to S phase of the cell cycle to repair broken chromatids and prevent iHR. Increased HR activity in G 0 arrested primary FLT3-ITD NK-AML in contrast to wild-type FLT3 NK-AML. Cells expressing mutated FLT3-ITD demonstrated a relative increase in mutation frequency as detected by thymidine kinase (TK) gene mutation assay. Moreover, resistance was associated with CN-LOH at the TK locus. Treatment of FLT3-ITD- and JAK2V617F-mutant cells with the antioxidant N -acetylcysteine diminished reactive oxygen species (ROS), restoring iHR and HR levels. Our findings show that mutated FLT3-ITD and JAK2 augment ROS production and HR, shifting the cellular milieu toward illegitimate recombination events such as iHR and CN-LOH. Therapeutic reduction of ROS may thus prevent leukemic progression and relapse in myeloid malignancies. Cancer Res; 77(7); 1697-708. ©2017 AACR . ©2017 American Association for Cancer Research.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28817615','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28817615"><span>Genotoxic effects of Roundup Full II® on lymphocytes of Chaetophractus villosus (Xenarthra, Mammalia): In vitro studies.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Luaces, Juan Pablo; Rossi, Luis Francisco; Chirino, Mónica Gabriela; Browne, Melanie; Merani, María Susana; Mudry, Marta Dolores</p>
<p>2017-01-01</p>
<p>In Argentina, Chaetophractus villosus has a wide distribution that overlaps with agricultural areas where soybean is the predominant crop. In such areas the pesticide Roundup Full II® (RU) is widely applied. The genotoxic effect of its active ingredient glyphosate (RU is 66.2% glyphosate) on the peripheral blood lymphocytes of C. villosus was tested over a range of concentrations (280, 420, 560, 1120 μmol/L). Culture medium without glyphosate served as negative control, while medium containing mitomycin C served as positive control. Genetic damage was characterized in terms of the percentage of cells with chromosome aberrations (CA), the mean number of sister chromatid exchanges (SCE) per cell, and the modification of cell proliferation kinetics via the calculation of the replication index. Significant increases (p < 0.0001) were seen in the CA frequency and the mean number of SCEs per cell compared to negative controls at all the RU concentrations tested. Chromatid breaks, the only form of CA observed, under the 560 μmol/L RU conditions and in presence of mitomycin C were four to five times more common than at lower concentrations, while no viable cells were seen in the 1120 μmol/L treatment. The mean number of SCEs per cell was significantly higher under the 280 μmol/L RU conditions than the 420 or 560 μmol/L RU conditions; cells cultivated in the presence of MMC also showed significantly more SCEs. All the RU concentrations tested (except in the 1120 μmol/L RU treatment [no viable cells]) induced a significant reduction in the replication index (p < 0.0001). The present results confirm the genotoxic effects of RU on C. villosus lymphocytes in vitro, strongly suggesting that exposure to RU could induce DNA damage in C. villosus wildlife.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21543101','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21543101"><span>Influence of GSTM1 and GSTT1 genotypes and confounding factors on the frequency of sister chromatid exchange and micronucleus among road construction workers.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Kumar, Anil; Yadav, Anita; Giri, Shiv Kumar; Dev, Kapil; Gautam, Sanjeev Kumar; Gupta, Ranjan; Aggarwal, Neeraj</p>
<p>2011-07-01</p>
<p>In the present study, we have investigated the influence of polymorphism of GSTM1 and GSTT1 genes and confounding factors such as age, sex, exposure duration and consumption habits on cytogenetic biomarkers. Frequency of sister chromatid exchanges (SCEs), high frequency cell (HFC) and cytokinesis blocked micronuclei (CBMN) were evaluated in peripheral blood lymphocytes of 115 occupationally exposed road construction workers and 105 unexposed individuals. The distribution of null and positive genotypes of glutathione-S transferase gene was evaluated by multiplex PCR among control and exposed subjects. An increased frequency of CBMN (7.03±2.08); SCE (6.95±1.76) and HFC (6.28±1.69) were found in exposed subjects when compared to referent (CBMN - 3.35±1.10; SCE - 4.13±1.30 and HFC - 3.98±1.56). These results were found statistically significant at p<0.05. When the effect of confounding factors on the frequency of studied biomarkers was evaluated, a strong positive interaction was found. The individuals having GSTM1 and GSTT1 null genotypes had higher frequency of CBMN, SCE and HFC. The association between GSTM1 and GSTT1 genotypes and studied biomarkers was found statistically significant at p<0.05. Our findings suggest that individuals having null type of GST are more susceptible to cytogenetic damage by occupational exposure regardless of confounding factors. There is a significant effect of polymorphism of these genes on cytogenetic biomarkers which are considered as early effects of genotoxic carcinogens. Copyright © 2011 Elsevier Ltd. All rights reserved.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/servlets/purl/6440856','SCIGOV-STC'); return false;" href="https://www.osti.gov/servlets/purl/6440856"><span></span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Harrison, F.L.; Rice, D.W. Jr., Moore, D.H.</p>
<p></p>
<p>Traditional bioassays are unsuitable for assessing sublethal effects from ocean disposal of low-level radioactive waste because mortality and phenotypic responses are not anticipated. We compared the usefulness of chromosomal aberration and sister chromatid exchange (SCE) induction as measures of low-level radiation effects in a sediment-dwelling marine worm, Neanthes arenaceodentata. The SCEs, in contrast to chromosomal aberrations, do not alter the overall chromosome morphology and in mammalian cells appear to be a more sensitive indicator of DNA alterations caused by environmental mutagens. Newly hatched larvae were exposed to two radiation-exposure regimes of either x rays at a high dose rate ofmore » 0.7 Gy (70 rad)/min for as long as 5.5 min or to /sup 60/Co gamma rays at a low dose rate of from 4.8 x 10/sup -5/ to 1.2 x 10/sup -1/ Gy (0.0048 to 12 rad)/h for 24 h. After irradiation, the larvae were exposed to 3 x 10/sup -5/M bromodeoxyuridine (BrdUrd) for 28 h (x-ray-irradiated larvae) or for 54 h (/sup 60/Co-irradiated larvae). Larval cells were examined for the proportion of cells in first, second, and third or greater division. Frequencies of chromosomal aberrations and SCEs were determined in first and second division cells, respectively. Results from x-ray irradiation indicated that dose-related increases occur in chromosome and chromatid deletions, but a dose of equal or greater 2 Gy (equal to or greater than 200 rad) was required to observe a significant increase. Worm larvae receiving /sup 60/Co irradiation showed elevated SCE frequencies with a significant increase of 0.6 Gy (60 rad). We suggest that both SCEs and chromosomal aberrations may be useful for measuring effects on genetic material induced by radiation. 56 references, 7 figures, 9 tables.« less</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3824207','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3824207"><span>Arabidopsis CHROMOSOME TRANSMISSION FIDELITY 7 (AtCTF7/ECO1) is required for DNA repair, mitosis and meiosis</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Bolaños-Villegas, Pablo; Yang, Xiaohui; Wang, Huei-Jing; Juan, Chien-Ta; Chuang, Min-Hsiang; Makaroff, Christopher A; Jauh, Guang-Yuh</p>
<p>2013-01-01</p>
<p>The proper transmission of DNA in dividing cells is crucial for the survival of eukaryotic organisms. During cell division, faithful segregation of replicated chromosomes requires their tight attachment, known as sister chromatid cohesion, until anaphase. Sister chromatid cohesion is established during S-phase in a process requiring an acetyltransferase that in yeast is known as Establishment of cohesion 1 (Eco1). Inactivation of Eco1 typically disrupts chromosome segregation and homologous recombination-dependent DNA repair in dividing cells, ultimately resulting in lethality. We report here the isolation and detailed characterization of two homozygous T-DNA insertion mutants for the Arabidopsis thaliana Eco1 homolog, CHROMOSOME TRANSMISSION FIDELITY 7/ESTABLISHMENT OF COHESION 1 (CTF7/ECO1), called ctf7-1 and ctf7-2. Mutants exhibited dwarfism, poor anther development and sterility. Analysis of somatic tissues by flow cytometry, scanning electron microscopy and quantitative real-time PCR identified defects in DNA repair and cell division, including an increase in the area of leaf epidermal cells, an increase in DNA content and the upregulation of genes involved in DNA repair including BRCA1 and PARP2. No significant change was observed in the expression of genes that influence entry into the endocycle. Analysis of meiocytes identified changes in chromosome morphology and defective segregation; the abundance of chromosomal-bound cohesion subunits was also reduced. Transcript levels for several meiotic genes, including the recombinase genes DMC1 and RAD51C and the S-phase licensing factor CDC45 were elevated in mutant anthers. Taken together our results demonstrate that Arabidopsis CTF7/ECO1 plays important roles in the preservation of genome integrity and meiosis. PMID:23750584</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4298131','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4298131"><span>From equator to pole: splitting chromosomes in mitosis and meiosis</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Duro, Eris</p>
<p>2015-01-01</p>
<p>During eukaryotic cell division, chromosomes must be precisely partitioned to daughter cells. This relies on a mechanism to move chromosomes in defined directions within the parental cell. While sister chromatids are segregated from one another in mitosis and meiosis II, specific adaptations enable the segregation of homologous chromosomes during meiosis I to reduce ploidy for gamete production. Many of the factors that drive these directed chromosome movements are known, and their molecular mechanism has started to be uncovered. Here we review the mechanisms of eukaryotic chromosome segregation, with a particular emphasis on the modifications that ensure the segregation of homologous chromosomes during meiosis I. PMID:25593304</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/7935987','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/7935987"><span>Evaluation of chemopreventive effects of betel leaf on the genotoxicity of pan masala.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Trivedi, A H; Patel, R K; Rawal, U M; Adhvaryu, S G; Balar, D B</p>
<p>1994-01-01</p>
<p>The antigenotoxic effect of the aqueous extract of betel leaf (BL-ext.) against the pan masala was tested with the help of cytogenetic endpoints like chromosome aberration (CA) and sister chromatid exchange (SCE) utilizing Chinese hamster ovary (CHO) cells. Compared to the cultures treated with aqueous extract of pan masala alone, a reduction in CA and SCE frequencies in CHO cells was observed following a combined treatment with pan masala (with or without tobacco) extract and BL-ext. The protective effect of BL-ext. against the genomic damage caused by pan masala was statistically significant only after treating the cells for a longer period.</p>
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</ol>
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<ol class="result-class" start="281">
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1015503','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1015503"><span>Familial polyposis coli: no evidence for increased sensitivity to mitomycin C.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Mazzullo, H A; Attwood, J; Delhanty, J D</p>
<p>1988-01-01</p>
<p>Spontaneous chromosome instability is well established for the dominantly inherited cancer prone condition, familial polyposis coli (FPC), but conflicting results have been obtained regarding sensitivity to mitomycin C (MMC). We have investigated cell survival in fibroblasts and the induction of sister chromatid exchanges and chromosome damage in lymphocytes and fibroblasts after MMC treatment. We can find no evidence for a differential response of FPC cells as measured by any of these parameters, although individual FPC fibroblast cultures did show an enhanced chromosomal response. Overall, the FPC mutation does not appear to result in defective DNA repair in response to MMC. PMID:2835481</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1213849','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1213849"><span>Absence of Interference in Association with Gene Conversion in SORDARIA FIMICOLA, and Presence of Interference in Association with Ordinary Recombination</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Kitani, Y.</p>
<p>1978-01-01</p>
<p>From the analysis of large samples of gene conversion asci in the g locus of Sordaria fimicola, it was found that neither the conversion event itself nor conversion-associated recombination of flanking markers cause either chiasma or chromatid interference with crossing over in a neighboring interval. The presence of more than one kind of crossover event, one causing interference the other not, is considered. The existence of two kinds of gene loci, one of single-cistron composition and the other of multiple-cistron composition, is discussed in relation to reciprocal recombination within a locus. PMID:17176535</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17176535','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17176535"><span>Absence of interference in association with gene conversion in Sordaria fimicola, and presence of interference in association with ordinary recombination.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Kitani, Y</p>
<p>1978-07-01</p>
<p>From the analysis of large samples of gene conversion asci in the g locus of Sordaria fimicola, it was found that neither the conversion event itself nor conversion-associated recombination of flanking markers cause either chiasma or chromatid interference with crossing over in a neighboring interval. The presence of more than one kind of crossover event, one causing interference the other not, is considered. The existence of two kinds of gene loci, one of single-cistron composition and the other of multiple-cistron composition, is discussed in relation to reciprocal recombination within a locus.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/9066660','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/9066660"><span>Antineoplastic and cytogenetic effects of complexes of Pd (II) with 4N-substituted derivatives of 2-acetyl-pyridine-thiosemicarbazone.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Papageorgiou, A; Iakovidou, Z; Mourelatos, D; Mioglou, E; Boutis, L; Kotsis, A; Kovala-Demertzi, D; Domopoulou, A; West, D X; Dermetzis, M A</p>
<p>1997-01-01</p>
<p>The effect of novel Pd(II) complexes with derivatives of 2-acetyl-pyridinethisemicarbazone, N4-ethyl (HAc4Et) and 3-hexamethyleneiminylthiosemicarbazone (HAchexim), on Sister Chromatid Exchange (SCE) rates and human lymphocyte proliferation kinetics was studied. Also, the effect of Pd(II) complexes on DNA synthesis of P388 and L1210 cell cultures and against Leukemia P388 was investigated. Among these compounds, the compound Bis(3-hexamethyleneiminyl-2-acetylpyridine-thisemicarbazonato++ +) palladium (II) was found to be distinctly effective against Leukemia P388, in inhibiting incorporation of 3H-thymidine into DNA and in inducing SCEs and cell division delays.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4227238','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4227238"><span>Calcium Signaling and Meiotic Exit at Fertilization in Xenopus Egg</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Tokmakov, Alexander A.; Stefanov, Vasily E.; Iwasaki, Tetsushi; Sato, Ken-Ichi; Fukami, Yasuo</p>
<p>2014-01-01</p>
<p>Calcium is a universal messenger that mediates egg activation at fertilization in all sexually reproducing species studied. However, signaling pathways leading to calcium generation and the mechanisms of calcium-induced exit from meiotic arrest vary substantially among species. Here, we review the pathways of calcium signaling and the mechanisms of meiotic exit at fertilization in the eggs of the established developmental model, African clawed frog, Xenopus laevis. We also discuss calcium involvement in the early fertilization-induced events in Xenopus egg, such as membrane depolarization, the increase in intracellular pH, cortical granule exocytosis, cortical contraction, contraction wave, cortical rotation, reformation of the nuclear envelope, sperm chromatin decondensation and sister chromatid segregation. PMID:25322156</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4412965','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4412965"><span>DNA Secondary Structure at Chromosomal Fragile Sites in Human Disease</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Thys, Ryan G; Lehman, Christine E; Pierce, Levi C. T; Wang, Yuh-Hwa</p>
<p>2015-01-01</p>
<p>DNA has the ability to form a variety of secondary structures that can interfere with normal cellular processes, and many of these structures have been associated with neurological diseases and cancer. Secondary structure-forming sequences are often found at chromosomal fragile sites, which are hotspots for sister chromatid exchange, chromosomal translocations, and deletions. Structures formed at fragile sites can lead to instability by disrupting normal cellular processes such as DNA replication and transcription. The instability caused by disruption of replication and transcription can lead to DNA breakage, resulting in gene rearrangements and deletions that cause disease. In this review, we discuss the role of DNA secondary structure at fragile sites in human disease. PMID:25937814</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28358361','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28358361"><span>Tumor-treating fields elicit a conditional vulnerability to ionizing radiation via the downregulation of BRCA1 signaling and reduced DNA double-strand break repair capacity in non-small cell lung cancer cell lines.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Karanam, Narasimha Kumar; Srinivasan, Kalayarasan; Ding, Lianghao; Sishc, Brock; Saha, Debabrata; Story, Michael D</p>
<p>2017-03-30</p>
<p>The use of tumor-treating fields (TTFields) has revolutionized the treatment of recurrent and newly diagnosed glioblastoma (GBM). TTFields are low-intensity, intermediate frequency, alternating electric fields that are applied to tumor regions and cells using non-invasive arrays. The predominant mechanism by which TTFields are thought to kill tumor cells is the disruption of mitosis. Using five non-small cell lung cancer (NSCLC) cell lines we found that there is a variable response in cell proliferation and cell killing between these NSCLC cell lines that was independent of p53 status. TTFields treatment increased the G2/M population, with a concomitant reduction in S-phase cells followed by the appearance of a sub-G1 population indicative of apoptosis. Temporal changes in gene expression during TTFields exposure was evaluated to identify molecular signaling changes underlying the differential TTFields response. The most differentially expressed genes were associated with the cell cycle and cell proliferation pathways. However, the expression of genes found within the BRCA1 DNA-damage response were significantly downregulated (P<0.05) during TTFields treatment. DNA double-strand break (DSB) repair foci increased when cells were exposed to TTFields as did the appearance of chromatid-type aberrations, suggesting an interphase mechanism responsible for cell death involving DNA repair. Exposing cells to TTFields immediately following ionizing radiation resulted in increased chromatid aberrations and a reduced capacity to repair DNA DSBs, which were likely responsible for at least a portion of the enhanced cell killing seen with the combination. These findings suggest that TTFields induce a state of 'BRCAness' leading to a conditional susceptibility resulting in enhanced sensitivity to ionizing radiation and provides a strong rationale for the use of TTFields as a combined modality therapy with radiation or other DNA-damaging agents.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11287300','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11287300"><span>Frequency of sister-chromatid exchange among greenhouse farmers exposed to pesticides.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Shaham, J; Kaufman, Z; Gurvich, R; Levi, Z</p>
<p>2001-04-05</p>
<p>Sister-chromatid exchange (SCE) was measured in peripheral lymphocytes of 104 greenhouse farmers exposed to pesticides and 44 unexposed workers. The results of SCEs are expressed in two variables: (a) mean number of SCEs per chromosome and, (b) proportion of high frequency cells (cells with more than eight SCEs). A high correlation was found between these two variables. The adjusted means of both SCEs variables were significantly higher among the farmers compared with the unexposed group (P < 0.01). Adjustment was made for smoking, age, education, and origin. The adjusted means of both SCE variables, were significantly elevated (P < 0.05) among the farmers who prepared and applied more than 70% of the pesticides by themselves compared with those who prepared and applied less than 70% of the pesticides by themselves. Both SCEs variables were also significantly elevated (P < 0.05) among farmers who were involved in more than 7.4 sprays per year compared with those with 7.4 or less sprays per year (P < 0.05). We found a tendency towards elevation of the two variables of SCEs among those who did not use protective measures while preparing the pesticides. Evaluation of the influence of years of exposure on the frequency of SCEs showed that the two variables of SCEs were higher among those farmers who were exposed to pesticides for more than 21 years than among those with less than 21 years of exposure. The variables that had the most influence on the elevation of SCEs were self-preparation of the pesticide mixtures and the number of sprayings per year. Because the farmers used a mixture of almost 24 different chemical classes it was impossible to attribute exposure to a specific pesticide or group of pesticides to single farmers. Our finding of a significant increase of SCEs frequency in peripheral lymphocytes in greenhouse farmers indicates a potential cytogenetic hazard due to pesticides exposure.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2016IJBm...60..873K','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2016IJBm...60..873K"><span>Assessment of adaptability of zebu cattle ( Bos indicus) breeds in two different climatic conditions: using cytogenetic techniques on genome integrity</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p>
<p>Kumar, Anil; Waiz, Syma Ashraf; Sridhar Goud, T.; Tonk, R. K.; Grewal, Anita; Singh, S. V.; Yadav, B. R.; Upadhyay, R. C.</p>
<p>2016-06-01</p>
<p>The aim of this study was to evaluate the genome integrity so as to assess the adaptability of three breeds of indigenous cattle reared under arid and semi-arid regions of Rajasthan (Bikaner) and Haryana (Karnal) India. The cattle were of homogenous group (same age and sex) of indigenous breeds viz. Sahiwal, Tharparkar and Kankrej. A total of 100 animals were selected for this study from both climatic conditions. The sister chromatid exchanges (SCE's), chromosomal gaps and chromatid breaks were observed in metaphase plates of chromosome preparations obtained from in vitro culture of peripheral blood lymphocytes. The mean number of breaks and gaps in Sahiwal and Tharparkar of semi-arid zone were 8.56 ± 3.16, 6.4 ± 3.39 and 8.72 ± 2.04, 3.52 ± 6.29, respectively. Similarly, the mean number of breaks and gaps in Tharparkar and Kankrej cattle of arid zone were 5.26 ± 1.76, 2.74 ± 1.76 and 5.24 ± 1.84, 2.5 ± 1.26, respectively. The frequency of SCEs in chromosomes was found significantly higher ( P < 0.05) in Tharparkar of semi-arid region (4.72 ± 1.55) compared to arid region (2.83 ± 1.01). Similarly, the frequency of SCEs was found to be 4.0 ± 1.41 in the Sahiwal of semi-arid region and 2.69 ± 1.12 in Kankrej of arid zone. Statistical analysis revealed significant differences ( P < 0.05) amongst the different zones, i.e. arid and semi-arid, whereas no significant difference ( P > 0.05) was observed in the same zone. The analysis of frequency of CAs and SCEs revealed significant effects of environmental conditions on the genome integrity of animals, thereby indicating an association with their adaptability.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2893262','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2893262"><span>Influence of homologous recombinational repair on cell survival and chromosomal aberration induction during the cell cycle in γ-irradiated CHO cells</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Wilson, Paul F.; Hinz, John M.; Urbin, Salustra S.; Nham, Peter B.; Thompson, Larry H.</p>
<p>2010-01-01</p>
<p>The repair of DNA double-strand breaks (DSB) by homologous recombinational repair (HRR) underlies the high radioresistance and low mutability observed in S-phase mammalian cells. To evaluate the contributions of HRR and nonhomologous end-joining (NHEJ) to overall DSB repair capacity throughout the cell cycle after γ-irradiation, we compared HRR-deficient RAD51D-knockout 51D1 to CgRAD51D-complemented 51D1 (51D1.3) CHO cells for survival and chromosomal aberrations (CAs). Asynchronous cultures were irradiated with 150 or 300 cGy and separated by cell size using centrifugal elutriation. Cell survival of each synchronous fraction (~20 fractions total from early G1 to late G2/M) was measured by colony formation. 51D1.3 cells were most resistant in S, while 51D1 cells were most resistant in early G1 (with survival and chromosome-type CA levels similar to 51D1.3) and became progressively more sensitive throughout S and G2. Both cell lines experienced significantly reduced survival from late S into G2. Metaphases were collected from every third elutriation fraction at the first post-irradiation mitosis and scored for CAs. 51D1 cells irradiated in S and G2 had ~2-fold higher chromatid-type CAs and a remarkable ~25-fold higher level of complex chromatid-type exchanges compared to 51D1.3 cells. Complex exchanges in 51D1.3 cells were only observed in G2. These results show an essential role for HRR in preventing gross chromosomal rearrangements in proliferating cells and, with our previous report of reduced survival of G2-phase NHEJ-deficient prkdc CHO cells [Hinz et al. DNA Repair 4, 782–792, 2005], imply reduced activity/efficiency of both HRR and NHEJ as cells transition from S to G2. PMID:20434408</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19545645','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19545645"><span>Chromosomal aberrations in a fish, Channa punctata after in vivo exposure to three heavy metals.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Yadav, Kamlesh K; Trivedi, Sunil P</p>
<p>2009-08-01</p>
<p>The studies were designed to assess the extent of chromosomal aberrations (CA) under the exposure of three common heavy metalic compounds, viz. mercuric chloride, arsenic trioxide and copper sulphate pentahydrate, in vivo using fish, Channa punctata (2n=32), as a test model. Prior acclimatized fishes were divided into five groups. Group I and II served as negative and positive control, respectively. An intramuscular injection of Mitomycin-C (@ 1mg/kg body wt.) was administered to group II only. Fishes of groups III, IV and V were subjected to sublethal concentrations (10% of 96h LC(50)), of HgCl(2) (0.081mg/L), As(2)O(3) (6.936mg/L) and CuSO(4)x5H(2)O (0.407mg/L). Fishes of all the groups were exposed uninterrupted for 24, 48, 72, 96 and 168h. Observations of kidney cells of exposed fishes revealed chromatid and chromosome breaks, chromatid and chromosome gaps along with ring and di-centric chromosomes. A significant increase over negative control in the frequency of chromosomal aberrations (CA) was observed in fish exposed to Mitomycin-C, Hg(II), As(III) and Cu(II). As the average + or - SE total number of CA, average number of CA per metaphase and %incidence of aberrant cells in Hg(II) was 104.40 + or - 8.189, 0.347 + or - 0.027 and 10.220 + or - 0.842, respectively; in As(III) 109.20 + or - 8.309, 0.363 + or - 0.027 and 10.820 + or - 2.347, respectively and in Cu(II) 89.00 + or - 19.066, 0.297 + or - 0.028 and 8.900 + or - 0.853, respectively. Hence, it reveals that the order of induction of frequency of CA was Cu<Hg<As. The findings depict genotoxic potential of these metals even in sublethal concentrations.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/3802407','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/3802407"><span>High local carcinogenic activity of 1,3-dimethyl-3-phenyl-1-nitrosourea and its inactivation by intravenous application in rats: comparison of in vivo findings with the in vitro direct and a combined in vivo/in vitro sister chromatid exchange assay in V79-E cells.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Thust, R; Martin, J; Mendel, J; Schreiber, D</p>
<p>1987-02-01</p>
<p>1,3-Dimethyl-3-phenyl-1-nitrosourea (DMPNU) is a very potent local carcinogen in rats and induces a 100% frequency of forestomach carcinomas when applied i.g. in two different dosages (10 applications of 0.3 or 0.03 mmol/kg body wt, respectively, at 14-day intervals), but it is inactive upon i.v. administration (10 applications of 0.03 mmol/kg body wt at 14-day intervals). By means of the direct sister chromatid exchange (SCE) assay in V79-E cells in the presence of rat blood, serum or plasma, respectively, as well as by a 'host-mediated' SCE assay (in which the agent was given i.v. to rats, and blood taken from the animal was checked for the recovery of genotoxic activity in cell cultures), we tried to elucidate the unexpected lack of carcinogenic activity of i.v. DMPNU. The direct SCE assay revealed a drastic reduction of DMPNU genotoxicity by rat blood, serum or plasma, respectively, which is abolished by the esterase inhibitor diisopropylfluorophosphate. In the 'host-mediated' SCE assay a genotoxic activity of DMPNU was only recoverable after a very high i.v. dose and when the blood added to the cell cultures had been taken from the rat heart within 1 min after DMPNU administration in vivo. 1-Methyl-1-nitrosourea (MNU) and 1-methyl-3-phenyl-1-nitrosourea (MPNU) were used as positive controls in these experiments and also gave a lower response than theoretically expected, but the relative loss of activity with the latter compounds was much lower than with DMPNU. It is assumed that an esterase in rat blood effectively decomposes this trisubstituted nitrosourea. Problems of the novel 'host-mediated' SCE assay are discussed.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26476524','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26476524"><span>Assessment of adaptability of zebu cattle (Bos indicus) breeds in two different climatic conditions: using cytogenetic techniques on genome integrity.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Kumar, Anil; Waiz, Syma Ashraf; Sridhar Goud, T; Tonk, R K; Grewal, Anita; Singh, S V; Yadav, B R; Upadhyay, R C</p>
<p>2016-06-01</p>
<p>The aim of this study was to evaluate the genome integrity so as to assess the adaptability of three breeds of indigenous cattle reared under arid and semi-arid regions of Rajasthan (Bikaner) and Haryana (Karnal) India. The cattle were of homogenous group (same age and sex) of indigenous breeds viz. Sahiwal, Tharparkar and Kankrej. A total of 100 animals were selected for this study from both climatic conditions. The sister chromatid exchanges (SCE's), chromosomal gaps and chromatid breaks were observed in metaphase plates of chromosome preparations obtained from in vitro culture of peripheral blood lymphocytes. The mean number of breaks and gaps in Sahiwal and Tharparkar of semi-arid zone were 8.56 ± 3.16, 6.4 ± 3.39 and 8.72 ± 2.04, 3.52 ± 6.29, respectively. Similarly, the mean number of breaks and gaps in Tharparkar and Kankrej cattle of arid zone were 5.26 ± 1.76, 2.74 ± 1.76 and 5.24 ± 1.84, 2.5 ± 1.26, respectively. The frequency of SCEs in chromosomes was found significantly higher (P < 0.05) in Tharparkar of semi-arid region (4.72 ± 1.55) compared to arid region (2.83 ± 1.01). Similarly, the frequency of SCEs was found to be 4.0 ± 1.41 in the Sahiwal of semi-arid region and 2.69 ± 1.12 in Kankrej of arid zone. Statistical analysis revealed significant differences (P < 0.05) amongst the different zones, i.e. arid and semi-arid, whereas no significant difference (P > 0.05) was observed in the same zone. The analysis of frequency of CAs and SCEs revealed significant effects of environmental conditions on the genome integrity of animals, thereby indicating an association with their adaptability.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/18820001','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/18820001"><span>A proteomic approach to identifying new drug targets (potentiating topoisomerase II poisons).</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Jenkins, J R</p>
<p>2008-10-01</p>
<p>Topoisomerase II poisons are an established part of best clinical practice for the treatment of a number of solid tumours and haematological malignancies. However, toxicity and resistance to chemotherapeutic drugs often complicate the treatment. Furthermore, topoisomerase II poisons can also induce sister chromatid exchange, chromosomal recombination and chromosome aberrations and are associated with a significant risk of secondary leukaemia. It would therefore be of great clinical benefit if the efficacy of topoisomerase II inhibitors could be enhanced without the increased toxic side effects. It is proposed that clinical agents targeting topoisomerase II can be enhanced by inhibiting proteins that modulate topoisomerase II. The aim is to identify proteins, that by the nature of their interaction with topoisomerase II, represent putative drug targets.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=19910018758&hterms=anemia&qs=N%3D0%26Ntk%3DAll%26Ntx%3Dmode%2Bmatchall%26Ntt%3Danemia','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=19910018758&hterms=anemia&qs=N%3D0%26Ntk%3DAll%26Ntx%3Dmode%2Bmatchall%26Ntt%3Danemia"><span>X ray sensitivity of diploid skin fibroblasts from patients with Fanconi's anemia</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p>
<p>Kale, Ranjini</p>
<p>1989-01-01</p>
<p>Experiments were performed on Fanconi's anemia and normal human fibroblast cell lines growing in culture in an attempt to correlate cell cycle kinetics with genomic damage and determine their bearing on the mechanism of chromosome aberration induction. FA fibroblasts showed a significantly increased susceptibility to chromosomal breakage by x rays in the G2 phase of the cell cycle. No such response was observed in fibroblasts irradiated in the G0 phase. The observed increases in achromatic lesions and in chromatid deletions in FA cells as compared with normal cells appear to indicate that FA cells are deficient in strand break repair and also possibly in base damage excision repair. Experiments are now in progress to further elucidate the mechanisms involved.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/2795466','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/2795466"><span>Comparative study on cytogenetic effects by diplatinum complexes of the ligands of naphthazarine and squaric acid in human lymphocytes.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Lialiaris, T; Mourelatos, D; Boutis, L; Papageorgiou, A; Christianopoulou, M; Papageorgiou, V; Dozi-Vassiliades, J</p>
<p>1989-10-01</p>
<p>The effect of diplatinum complexes of the binucleating ligands of naphthazarine and squaric acid on Sister Chromatid Exchange (SCE) rates and human lymphocyte proliferation kinetics was studied. Squarodicisplatinum complex I, naphthazarindicisplatinum and squarodicisplatinum complex II induce cytotoxic effects as can be deduced from the resulted induction of SCEs and the produced cell division delays. Squarodicisplatinum complex I was found to be on a molar basis the most effective in causing markedly increased SCE rates and cell division delays. Cis-diaminodichloride platinum was found to be next in order of effectiveness with naphthazarindicisplatinum and squarodicisplatinum complex II following. Naphthazarine and SQA were found to be ineffective on induction of SCEs.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/3342394','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/3342394"><span>Enhancement of cytogenetic damage and of antineoplastic effect by caffeine in Ehrlich ascites tumor cells treated with cyclophosphamide in vivo.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Mourelatos, D; Dozi-Vassiliades, J; Kotsis, A; Gourtsas, C</p>
<p>1988-03-01</p>
<p>Enhanced cytogenetic damage by cyclophosphamide (CP) was observed when Ehrlich ascites tumor cells were exposed in vivo to nontoxic concentrations of caffeine. One h before i.p. injection of 5-bromodeoxyuridine adsorbed to activated charcoal Ehrlich ascites tumor-bearing mice treated i.p. with CP appear to have a dose-dependent increase in sister chromatid exchange rates and cell division delays. Caffeine increased the survival time of the Ehrlich ascites tumor-bearing mice treated with CP and markedly reduced the ascitic volume. Therefore, the in vivo antitumor effect by CP in conjunction with caffeine appears to correlate well with the in vivo synergistic effect on cytogenetic damage caused by the combined CP plus caffeine treatment.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11272288','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11272288"><span>Platinum(II) and palladium(II) complexes with 2-acetylpyridine thiosemicarbazone: cytogenetic and antineoplastic effects.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Lakovidou, Z; Papageorgiou, A; Demertzis, M A; Mioglou, E; Mourelatos, D; Kotsis, A; Yadav, P N; Kovala-Demertzi, D</p>
<p>2001-01-01</p>
<p>The effect of three novel complexes of Pt(II) and three complexes of Pd(II) with 2-acetylpyridine thiosemicarbazone (HAcTsc) on sister chromatid exchange (SCE) rates and human lymphocyte proliferation kinetics on a molar basis was studied. Also, the effect of Pt(II) and Pd(II) complexes against leukemia P388 was investigated. Among these compounds, the most effective in inducing antitumor and cytogenetic effects were the complexes [Pt(AcTsc)2] x H2O and [Pd(AcTsc)2] while the rest, i.e. (HAcTsc), [Pt(AcTsc)Cl], [Pt(HAcTsc)2]Cl2 x 2H2O, [Pd(AcTsc)Cl] and [Pd(HAcTsc)2]Cl2, displayed marginal cytogenetic and antitumor effects.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26648952','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26648952"><span>Structure and Function of Centromeric and Pericentromeric Heterochromatin in Arabidopsis thaliana.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Simon, Lauriane; Voisin, Maxime; Tatout, Christophe; Probst, Aline V</p>
<p>2015-01-01</p>
<p>The centromere is a specific chromosomal region where the kinetochore assembles to ensure the faithful segregation of sister chromatids during mitosis and meiosis. Centromeres are defined by a local enrichment of the specific histone variant CenH3 mostly at repetitive satellite sequences. A larger pericentromeric region containing repetitive sequences and transposable elements surrounds the centromere that adopts a particular chromatin state characterized by specific histone variants and post-translational modifications and forms a transcriptionally repressive chromosomal environment. In the model organism Arabidopsis thaliana centromeric and pericentromeric domains form conspicuous heterochromatin clusters called chromocenters in interphase. Here we discuss, using Arabidopsis as example, recent insight into mechanisms involved in maintenance and establishment of centromeric and pericentromeric chromatin signatures as well as in chromocenter formation.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3801442','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3801442"><span>How unfinished business from S-phase affects mitosis and beyond</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Mankouri, Hocine W; Huttner, Diana; Hickson, Ian D</p>
<p>2013-01-01</p>
<p>The eukaryotic cell cycle is conventionally viewed as comprising several discrete steps, each of which must be completed before the next one is initiated. However, emerging evidence suggests that incompletely replicated, or unresolved, chromosomes from S-phase can persist into mitosis, where they present a potential threat to the faithful segregation of sister chromatids. In this review, we provide an overview of the different classes of loci where this ‘unfinished S-phase business' can lead to a variety of cytogenetically distinct DNA structures throughout the various steps of mitosis. Furthermore, we discuss the potential ways in which cells might not only tolerate this inevitable aspect of chromosome biology, but also exploit it to assist in the maintenance of genome stability. PMID:24065128</p>
</li>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24065128','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24065128"><span>How unfinished business from S-phase affects mitosis and beyond.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Mankouri, Hocine W; Huttner, Diana; Hickson, Ian D</p>
<p>2013-10-16</p>
<p>The eukaryotic cell cycle is conventionally viewed as comprising several discrete steps, each of which must be completed before the next one is initiated. However, emerging evidence suggests that incompletely replicated, or unresolved, chromosomes from S-phase can persist into mitosis, where they present a potential threat to the faithful segregation of sister chromatids. In this review, we provide an overview of the different classes of loci where this 'unfinished S-phase business' can lead to a variety of cytogenetically distinct DNA structures throughout the various steps of mitosis. Furthermore, we discuss the potential ways in which cells might not only tolerate this inevitable aspect of chromosome biology, but also exploit it to assist in the maintenance of genome stability.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4495907','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4495907"><span>The roles of cohesins in mitosis, meiosis, and human health and disease</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Brooker, Amanda S.; Berkowitz, Karen M.</p>
<p>2015-01-01</p>
<p>Summary Mitosis and meiosis are essential processes that occur during development. Throughout these processes, cohesion is required to keep the sister chromatids together until their separation at anaphase. Cohesion is created by multi-protein subunit complexes called cohesins. Although the subunits differ slightly in mitosis and meiosis, the canonical cohesin complex is composed of four subunits that are quite diverse. The cohesin complexes are also important for DNA repair, gene expression, development, and genome integrity. Here we provide an overview of the roles of cohesins during these different events, as well as their roles in human health and disease, including the cohesinopathies. Although the exact roles and mechanisms of these proteins are still being elucidated, this review will serve as a guide for the current knowledge of cohesins. PMID:24906316</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19878742','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19878742"><span>The importance of chromosome studies in Roberts syndrome/SC phocomelia and other cohesinopathies.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Gerkes, Erica H; van der Kevie-Kersemaekers, Anne-Marie F; Yakin, Mariam; Smeets, Dominique F C M; van Ravenswaaij-Arts, Conny M A</p>
<p>2010-01-01</p>
<p>Roberts syndrome/SC phocomelia is a rare, autosomal recessive syndrome characterised by pre- and postnatal growth retardation, microcephaly, craniofacial anomalies, mental retardation, and tetraphocomelia in varying degrees of severity. The clinical diagnosis can be challenging in phenotypically mild cases. In the extremely mild case presented here, specific mitotic abnormalities were detected and proved to be very helpful, since Roberts syndrome/SC phocomelia could be diagnosed after finding premature centromere separation and somatic aneuploidy at routine karyotyping. We discuss these and other mitotic cytogenetic abnormalities that can be of significant diagnostic importance, but which will be missed if only array studies are performed. We also discuss the difference between premature centromere separation and premature (sister) chromatid separation. Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/18996191','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/18996191"><span>Stem cell identity and template DNA strand segregation.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Tajbakhsh, Shahragim</p>
<p>2008-12-01</p>
<p>The quest for stem cell properties to distinguish their identity from that of committed daughters has led to a re-investigation of the notion that DNA strands are not equivalent, and 'immortal' DNA strands are retained in stem cells whereas newly replicated DNA strands segregate to the differentiating daughter cell during mitosis. Whether this process occurs only in stem cells, and also in all tissues, remains unclear. That individual chromosomes can be also partitioned non-randomly raises the question if this phenomenon is related to the immortal DNA hypothesis, and it underscores the need for high-resolution techniques to observe these events empirically. Although initially postulated as a mechanism to avoid DNA replication errors, alternative views including epigenetic regulation and sister chromatid silencing may provide insights into this process.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28631016','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28631016"><span>New insights into cohesin loading.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Litwin, Ireneusz; Wysocki, Robert</p>
<p>2018-02-01</p>
<p>Cohesin is a conserved, ring-shaped protein complex that encircles sister chromatids and ensures correct chromosome segregation during mitosis and meiosis. It also plays a crucial role in the regulation of gene expression, DNA condensation, and DNA repair through both non-homologous end joining and homologous recombination. Cohesins are spatiotemporally regulated by the Scc2-Scc4 complex which facilitates cohesin loading onto chromatin at specific chromosomal sites. Over the last few years, much attention has been paid to cohesin and cohesin loader as it became clear that even minor disruptions of these complexes may lead to developmental disorders and cancers. Here we summarize recent developments in the structure of Scc2-Scc4 complex, cohesin loading process, and mediators that determine the Scc2-Scc4 binding patterns to chromatin.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20513141','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20513141"><span>The expanding universe of cohesin functions: a new genome stability caretaker involved in human disease and cancer.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Mannini, Linda; Menga, Stefania; Musio, Antonio</p>
<p>2010-06-01</p>
<p>Cohesin is responsible for sister chromatid cohesion, ensuring the correct chromosome segregation. Beyond this role, cohesin and regulatory cohesin genes seem to play a role in preserving genome stability and gene transcription regulation. DNA damage is thought to be a major culprit for many human diseases, including cancer. Our present knowledge of the molecular basis underlying genome instability is extremely limited. Mutations in cohesin genes cause human diseases such as Cornelia de Lange syndrome and Roberts syndrome/SC phocomelia, and all the cell lines derived from affected patients show genome instability. Cohesin mutations have also been identified in colorectal cancer. Here, we will discuss the human disorders caused by alterations of cohesin function, with emphasis on the emerging role of cohesin as a genome stability caretaker.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=20040088760&hterms=telomere&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D20%26Ntt%3Dtelomere','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=20040088760&hterms=telomere&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D20%26Ntt%3Dtelomere"><span>Characteristics of chromosome instability in the human lymphoblast cell line WTK1</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p>
<p>Schwartz, J. L.; Jordan, R.; Evans, H. H.</p>
<p>2001-01-01</p>
<p>The characteristics of spontaneous and radiation-induced chromosome instability were determined in each of 50 individual clones isolated from control populations of human lymphoblasts (WTK1), as well as from populations of these cells previously exposed to two different types of ionizing radiation, Fe-56 and Cs-137. The types of chromosome instability did not appear to change in clones surviving radiation exposure. Aneuploidy, polyploidy, chromosome dicentrics and translocations, and chromatid breaks and gaps were found in both control and irradiated clones. The primary effect of radiation exposure was to increase the number of cells within any one clone that had chromosome alterations. Chromosome instability was associated with telomere shortening and elevated levels of apoptosis. The results suggest that the proximal cause of chromosome instability is telomere shortening.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3423812','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3423812"><span>Microcystin-LR, a protein phosphatase inhibitor, induces alterations in mitotic chromatin and microtubule organization leading to the formation of micronuclei in Vicia faba</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Beyer, Dániel; Tándor, Ildikó; Kónya, Zoltán; Bátori, Róbert; Roszik, Janos; Vereb, György; Erdődi, Ferenc; Vasas, Gábor; M-Hamvas, Márta; Jambrovics, Károly; Máthé, Csaba</p>
<p>2012-01-01</p>
<p>Background and Aims Microcystin-LR (MCY-LR) is a cyanobacterial toxin, a specific inhibitor of type 1 and 2A protein phosphatases (PP1 and PP2A) with significant impact on aquatic ecosystems. It has the potential to alter regulation of the plant cell cycle. The aim of this study was improved understanding of the mitotic alterations induced by cyanotoxin in Vicia faba, a model organism for plant cell biology studies. Methods Vicia faba seedlings were treated over the long and short term with MCY-LR purified in our laboratory. Short-term treatments were performed on root meristems synchronized with hydroxylurea. Sections of lateral root tips were labelled for chromatin, phosphorylated histone H3 and β-tubulin via histochemical and immunohistochemical methods. Mitotic activity and the occurrence of mitotic alterations were detected and analysed by fluorescence microscopy. The phosphorylation state of histone H3 was studied by Western blotting. Key Results Long-term MCY-LR exposure of lateral root tip meristems increased the percentage of either early or late mitosis in a concentration-dependent manner. We observed hypercondensed chromosomes and altered sister chromatid segregation (lagging chromosomes) leading to the formation of micronuclei, accompanied by the formation of disrupted, multipolar and monopolar spindles, disrupted phragmoplasts and the hyperphosphorylation of histone H3 at Ser10. Short-term MCY-LR treatment of synchronized cells showed that PP1 and PP2A inhibition delayed the onset of anaphase at 1 µg mL−1 MCY-LR, accelerated cell cycle at 10 µg mL−1 MCY-LR and induced the formation of lagging chromosomes. In this case mitotic microtubule alterations were not detected, but histone H3 was hyperphosphorylated. Conclusions MCY-LR delayed metaphase–anaphase transition. Consequently, it induced aberrant chromatid segregation and micronucleus formation that could be associated with both H3 hyperphosphorylation and altered microtubule organization. However, these two phenomena seemed to be independent. The toxin may be a useful tool in the study of plant cell cycle regulation. PMID:22819947</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22819947','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22819947"><span>Microcystin-LR, a protein phosphatase inhibitor, induces alterations in mitotic chromatin and microtubule organization leading to the formation of micronuclei in Vicia faba.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Beyer, Dániel; Tándor, Ildikó; Kónya, Zoltán; Bátori, Róbert; Roszik, Janos; Vereb, György; Erdodi, Ferenc; Vasas, Gábor; M-Hamvas, Márta; Jambrovics, Károly; Máthé, Csaba</p>
<p>2012-09-01</p>
<p>Microcystin-LR (MCY-LR) is a cyanobacterial toxin, a specific inhibitor of type 1 and 2A protein phosphatases (PP1 and PP2A) with significant impact on aquatic ecosystems. It has the potential to alter regulation of the plant cell cycle. The aim of this study was improved understanding of the mitotic alterations induced by cyanotoxin in Vicia faba, a model organism for plant cell biology studies. Vicia faba seedlings were treated over the long and short term with MCY-LR purified in our laboratory. Short-term treatments were performed on root meristems synchronized with hydroxylurea. Sections of lateral root tips were labelled for chromatin, phosphorylated histone H3 and β-tubulin via histochemical and immunohistochemical methods. Mitotic activity and the occurrence of mitotic alterations were detected and analysed by fluorescence microscopy. The phosphorylation state of histone H3 was studied by Western blotting. Long-term MCY-LR exposure of lateral root tip meristems increased the percentage of either early or late mitosis in a concentration-dependent manner. We observed hypercondensed chromosomes and altered sister chromatid segregation (lagging chromosomes) leading to the formation of micronuclei, accompanied by the formation of disrupted, multipolar and monopolar spindles, disrupted phragmoplasts and the hyperphosphorylation of histone H3 at Ser10. Short-term MCY-LR treatment of synchronized cells showed that PP1 and PP2A inhibition delayed the onset of anaphase at 1 µg mL(-1) MCY-LR, accelerated cell cycle at 10 µg mL(-1) MCY-LR and induced the formation of lagging chromosomes. In this case mitotic microtubule alterations were not detected, but histone H3 was hyperphosphorylated. MCY-LR delayed metaphase-anaphase transition. Consequently, it induced aberrant chromatid segregation and micronucleus formation that could be associated with both H3 hyperphosphorylation and altered microtubule organization. However, these two phenomena seemed to be independent. The toxin may be a useful tool in the study of plant cell cycle regulation.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/7528334','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/7528334"><span>Comparative study on cytogenetic damage induced by homo-aza-steroidal esters in human lymphocytes.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Mourelatos, D; Papageorgiou, A; Boutis, L; Catsoulacos, P</p>
<p>1995-02-01</p>
<p>The effect of P[N,N-bis(2-chloroethyl)amino]phenylacetate esters of 3 beta-hydroxy-N-methyl-17 alpha-aza-D-homo-5 alpha-androstan-17-one (compound 3) and 3 beta-hydroxy-17 alpha-aza-D-homo-5 alpha-androstane (compound 2) on sister-chromatid exchange (SCE) frequencies and on human lymphocytes proliferation kinetics was studied. The results are compared with those of the P[N,N-bis(2-chloroethyl)amino]phenylacetate esters of 3 beta-hydroxy-17 alpha-aza-D-homo-5 alpha-androstan-17-one (compound 1). All compounds were found to be active in inducing markedly increased SCE rates and cell division delays. A correlation between potency for SCE induction, effectiveness in cell division delay and previously established antitumour activity of these compounds was observed.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3895905','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3895905"><span>A new paradigm for transcription factor TFIIB functionality</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Gelev, Vladimir; Zabolotny, Janice M.; Lange, Martin; Hiromura, Makoto; Yoo, Sang Wook; Orlando, Joseph S.; Kushnir, Anna; Horikoshi, Nobuo; Paquet, Eric; Bachvarov, Dimcho; Schaffer, Priscilla A.; Usheva, Anny</p>
<p>2014-01-01</p>
<p>Experimental and bioinformatic studies of transcription initiation by RNA polymerase II (RNAP2) have revealed a mechanism of RNAP2 transcription initiation less uniform across gene promoters than initially thought. However, the general transcription factor TFIIB is presumed to be universally required for RNAP2 transcription initiation. Based on bioinformatic analysis of data and effects of TFIIB knockdown in primary and transformed cell lines on cellular functionality and global gene expression, we report that TFIIB is dispensable for transcription of many human promoters, but is essential for herpes simplex virus-1 (HSV-1) gene transcription and replication. We report a novel cell cycle TFIIB regulation and localization of the acetylated TFIIB variant on the transcriptionally silent mitotic chromatids. Taken together, these results establish a new paradigm for TFIIB functionality in human gene expression, which when downregulated has potent anti-viral effects. PMID:24441171</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1456240','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1456240"><span>Diverse Mitotic and Interphase Functions of Condensins in Drosophila</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Cobbe, Neville; Savvidou, Ellada; Heck, Margarete M. S.</p>
<p>2006-01-01</p>
<p>The condensin complex has been implicated in the higher-order organization of mitotic chromosomes in a host of model eukaryotes from yeasts to flies and vertebrates. Although chromosomes paradoxically appear to condense in condensin mutants, chromatids are not properly resolved, resulting in chromosome segregation defects during anaphase. We have examined the role of different condensin complex components in interphase chromatin function by examining the effects of various condensin mutations on position-effect variegation in Drosophila melanogaster. Surprisingly, most mutations affecting condensin proteins were often found to result in strong enhancement of variegation in contrast to what might be expected for proteins believed to compact the genome. This suggests either that the role of condensin proteins in interphase differs from their expected role in mitosis or that the way we envision condensin's activity needs to be modified to accommodate alternative possibilities. PMID:16272408</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27752841','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27752841"><span>Antioxidant and antigenotoxic potencies of Sempervivum armenum on human lymphocytes in vitro.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Sunar, Serap; Anar, Mustafa; Sengul, Meryem; Agar, Guleray</p>
<p>2016-12-01</p>
<p>In this research, the genotoxic and antigenotoxic effects of methanol extract of Sempervivum armenum (MSA) were studied using micronucleus (MN) test and sister chromatid exchange (SCE) test systems in cultured human peripheral blood cells. According to the SCE and MN tests results, MSA reduced the genotoxic effects of aflatoxin B 1 . In order to explain the reason for the antigenotoxic effects of MSA, antioxidants levels were determined. Cotreatments of 5, 10, 20 mg/mL concentrations of MSA with aflatoxin B 1 decreased the frequencies of SCE, MN and the malondialdehyde level and increased the amount of superoxide dismutase, glutathione and glutathione peroxidase which were decreased by aflatoxin. The results of this experiment showed that MSA has strong antioxidative and antigenotoxic effects and this antigenotoxic activities of MSA can be due to the antioxidant activities.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/6256802','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/6256802"><span>Effects of 1.9 MeV monoenergetic neutrons on Vicia faba chromosomes: microdosimetric considerations.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Geard, C R</p>
<p>1980-01-01</p>
<p>Aerated Vicia faba root meristems were irradiated with 1.9 MeV monoenergetic neutrons. This source of neutrons optimally provides one class of particles (recoil protons) with ranges able to traverse cell nuclei at moderate to high-LET. The volumes of the Vicia faba nuclei were log-normally distributed with a mean of 1100 micrometer3. The yield of chromatid-type aberrations was linear against absorbed dose and near-constant over 5 collection periods (2-12 h), after irradiation. Energy deposition events (recoil protons) determined by microdosimetry were related to cytological changes with the finding that 19% of incident recoil protons initiate visible changes in Vicia faba chromosomes. It is probable that a substantial fraction of recoil proton track length and deposited energy is in insensitive (non-DNA containing) portions of the nuclear volume.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22665764','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22665764"><span>Reciprocal uniparental disomy in yeast.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Andersen, Sabrina L; Petes, Thomas D</p>
<p>2012-06-19</p>
<p>In the diploid cells of most organisms, including humans, each chromosome is usually distinguishable from its partner homolog by multiple single-nucleotide polymorphisms. One common type of genetic alteration observed in tumor cells is uniparental disomy (UPD), in which a pair of homologous chromosomes are derived from a single parent, resulting in loss of heterozygosity for all single-nucleotide polymorphisms while maintaining diploidy. Somatic UPD events are usually explained as reflecting two consecutive nondisjunction events. Here we report a previously undescribed mode of chromosome segregation in Saccharomyces cerevisiae in which one cell division produces daughter cells with reciprocal UPD for the same pair of chromosomes without an aneuploid intermediate. One pair of sister chromatids is segregated into one daughter cell and the other pair is segregated into the other daughter cell, mimicking a meiotic chromosome segregation pattern. We term this process "reciprocal uniparental disomy."</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20099979','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20099979"><span>X-irradiation of human bronchial cancer cells causes the bystander effects in normal bronchial cells in vitro.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Konopacka, M; Rogoliński, J</p>
<p>2010-01-01</p>
<p>Using X radiation commonly used in radiotherapy of cancers we investigated bystander interactions between human cells: irradiated A549 bronchial carcinoma human cells and non irradiated BEAS-2B normal bronchial epithelial cells. Non irradiated cells were incubated in medium transferred from irradiated A549 cells (ICM-irradiation conditioned medium) for 48h and next the chromosomal damage and apoptosis were estimated. Conditioned medium collected from irradiated cancer cells induced in non irradiated cells of the same line as well as in BEAS-2B normal cells genetic changes such as micronuclei, chromatid and chromosomal breaks and condensation of chromatin characteristic for processes of apoptosis. Addition of only 1% of conditioned medium to fresh medium was sufficient to induction of bystander response to normal bronchial cells. The presented results in this study could have implications for human radiation risk and in evaluating the secondary effects of radiotherapy.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5743930','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5743930"><span>The Ins and Outs of Aurora B Inner Centromere Localization</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Hindriksen, Sanne; Lens, Susanne M. A.; Hadders, Michael A.</p>
<p>2017-01-01</p>
<p>Error-free chromosome segregation is essential for the maintenance of genomic integrity during cell division. Aurora B, the enzymatic subunit of the Chromosomal Passenger Complex (CPC), plays a crucial role in this process. In early mitosis Aurora B localizes predominantly to the inner centromere, a specialized region of chromatin that lies at the crossroads between the inter-kinetochore and inter-sister chromatid axes. Two evolutionarily conserved histone kinases, Haspin and Bub1, control the positioning of the CPC at the inner centromere and this location is thought to be crucial for the CPC to function. However, recent studies sketch a subtler picture, in which not all functions of the CPC require strict confinement to the inner centromere. In this review we discuss the molecular pathways that direct Aurora B to the inner centromere and deliberate if and why this specific localization is important for Aurora B function. PMID:29312936</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('http://hdl.handle.net/2060/19750006311','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/19750006311"><span>Cytogenic studies of blood (experiment M111)</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p>
<p>Lockhart, L. H.</p>
<p>1974-01-01</p>
<p>The Skylab M111 experiment was a continuation of the preflight and postflight chromosomal analyses of the flight crews that have been performed since the Gemini 3 mission. The experiment was designed to determine whether some space flight parameter produces cytogenetic effects in human cells and to provide biological radiation dosimetric capability in the event of significant radiation exposure to a flight crew. On each of the Skylab flights, blood lymphocytes for analysis of chromosomes for structural defects were obtained from each of the prime crewmembers and from a ground-based control group before and after flight. Two types of defects were recorded. The minor defects included the following aberrations: chromatid fragments, chromosome fragments, and deletions. Structural rearrangements such as dicentrics, exchanges, ring chromosomes, and translocations were photographed, and the cells were karyotyped to delineate, when possible, the chromosome or chromosomes involved in the rearrangement. Result seems to indicate that the flight itself was not a major contributing factor.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3291308','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3291308"><span>Is cohesin required for spindle-pole-body/centrosome cohesion?</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Jin, Hui; Avey, Martin</p>
<p>2012-01-01</p>
<p>Centrosomes are microtubule-organizing centers that nucleate spindle microtubules during cell division. In budding yeast, the centrosome, often referred to as the spindle pole body, shares structural components with the centriole, the central core of the animal centrosome. The parental centrosome is duplicated when DNA replication takes place. Like sister chromatids tethered together by cohesin, duplicated centrosomes are linked and then separate to form the bipolar spindle necessary for chromosome segregation. Recent studies have shown that cohesin is also localized to the animal centrosome and is perhaps directly involved in engaging paired centrioles. Here we discuss the potential role of cohesin in mediating spindle-pole-body cohesion in the context of yeast meiosis. We propose that the coordination of chromosome segregation with centrosome cohesion and duplication is mediated by the antagonistic interaction between the Aurora kinase and the Polo kinase and that the role of cohesin in centrosome regulation appears to be indirect in budding yeast. PMID:22482005</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/12678382','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/12678382"><span>Chromosome aberration analysis in peripheral lymphocytes of Gulf War and Balkans War veterans.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Schröder, H; Heimers, A; Frentzel-Beyme, R; Schott, A; Hoffmann, W</p>
<p>2003-01-01</p>
<p>Chromosome aberrations and sister chromatid exchanges (SCEs) were determined in standard peripheral lymphocyte metaphase preparations of 13 British Gulf War veterans, two veterans of the recent war in the Balkans and one veteran of both wars. All 16 volunteers suspect exposures to depleted uranium (DU) while deployed at the two different theatres of war in 1990 and later on. The Bremen laboratory control served as a reference in this study. Compared with this control there was a statistically significant increase in the frequency of dicentric chromosomes (dic) and centric ring chromosomes (cR) in the veterans' group. indicating a previous exposure to ionising radiation. The statistically significant overdispersion of die and cR indicates non-uniform irradiation as would be expected after non-uniform exposure and/or exposure to radiation with a high linear energy transfer (LET). The frequency of SCEs was decreased when compared with the laboratory control.</p>
</li>
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<ol class="result-class" start="321">
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29332103','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29332103"><span>Proteomic effects of wet cupping (Al-hijamah).</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Almaiman, Amer A</p>
<p>2018-01-01</p>
<p>Wet cupping (Al-hijamah) is a therapeutic technique practiced worldwide as a part of the Unani system of medicine. It involves bloodletting from acupoints on a patient's skin to produce a therapeutic outcome. A thorough review of research articles on wet cupping with relevance to proteomics field that are indexed by Google Scholar, PubMed, and/or Science Direct databases was performed. Eight original research articles were summarized in this paper. Overall, wet cupping did not have a significant effect on C-reactive protein, Hsp-27, sister chromatid exchanges, and cell replication index. In contrast, wet cupping was found to produce higher oxygen saturation, eliminate lactate from subcutaneous tissues, remove blood containing higher levels of malondialdehyde and nitric oxide, and produce higher activity of myeloperoxidase. The proteomic effects of wet cupping therapy have not been adequately investigated. Thus, future studies on wet cupping that use systemic and sound protocols to avoid bias should be conducted.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5885108','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5885108"><span>Proteomic effects of wet cupping (Al-hijamah)</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Almaiman, Amer A.</p>
<p>2018-01-01</p>
<p>Wet cupping (Al-hijamah) is a therapeutic technique practiced worldwide as a part of the Unani system of medicine. It involves bloodletting from acupoints on a patient’s skin to produce a therapeutic outcome. A thorough review of research articles on wet cupping with relevance to proteomics field that are indexed by Google Scholar, PubMed, and/or Science Direct databases was performed. Eight original research articles were summarized in this paper. Overall, wet cupping did not have a significant effect on C-reactive protein, Hsp-27, sister chromatid exchanges, and cell replication index. In contrast, wet cupping was found to produce higher oxygen saturation, eliminate lactate from subcutaneous tissues, remove blood containing higher levels of malondialdehyde and nitric oxide, and produce higher activity of myeloperoxidase. The proteomic effects of wet cupping therapy have not been adequately investigated. Thus, future studies on wet cupping that use systemic and sound protocols to avoid bias should be conducted. PMID:29332103</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/9876211','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/9876211"><span>Enhanced cytogenetic and antineoplastic effects by the combined action of two esteric steroidal derivatives of nitrogen mustards.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Papageorgiou, A; Nikolaropoulos, S S; Arsenou, E S; Karaberis, E; Mourelatos, D; Kotsis, A; Chryssogelou, E</p>
<p>1999-01-01</p>
<p>The authors studied the effect of two modified steroids containing different proportions (%) of alkylating agents alone or in combination on sister chromatid exchange (SCE) rates and on human lymphocyte proliferation kinetics. The antitumor activity of these compounds was tested on leukemia P388- and leukemia L1210-bearing mice. The two chemicals in mixtures enhance SCE induction and antitumor activity in a synergistic manner. The homo-aza-steroidal ester of p-bis(2-chloroethyl)aminophenyl acetic acid was found to be more effective than the homo-aza-steroidal ester of o-bis(2-chloroethyl)aminobenzoic acid in causing cytogenetic damage and antineoplastic activity. A correlation was observed between the magnitude of the SCE response and the depression of the cell proliferation index. The order of the antitumor effectiveness of the five different treatments tested coincided with the order of the cytogenetic effects they induced.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1204473','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1204473"><span>The Molecular Structure of Te146 and Its Derivatives in Drosophila Melanogaster</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Lovering, R.; Harden, N.; Ashburner, M.</p>
<p>1991-01-01</p>
<p>TE146 is a giant transposon of Drosophila melanogaster. It carries two copies of the white and roughest genes, normally found on the X chromosome. The structure of this transposon has been studied at the molecular level. TE146 may transpose to new chromosome positions, excise and be lost from the genome or undergo internal rearrangements. The termini of TE146 are foldback DNA elements (FB); the transposon also carries two internal FB elements. Loss or internal rearrangement of TE146 involves recombination between different FB elements. These events have been mapped molecularly, by taking advantage of the fact that the FB sequences are composed largely of a regular 155-bp repeat sequence that is cut by the restriction enzyme TaqI, and are shown to be nonrandom. We suggest that these FB-FB exchange events occur by mitotic sister-chromatid exchange in the premeiotic germ line. PMID:1649070</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=49369','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=49369"><span>Stable transformation of a mosquito cell line results in extraordinarily high copy numbers of the plasmid.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Monroe, T J; Muhlmann-Diaz, M C; Kovach, M J; Carlson, J O; Bedford, J S; Beaty, B J</p>
<p>1992-01-01</p>
<p>Stable incorporation of high copy numbers (greater than 10,000 per cell) of a plasmid vector containing a gene conferring resistance to the antibiotic hygromycin was achieved in a cell line derived from the Aedes albopictus mosquito. Plasmid sequences were readily observed by ethidium bromide staining of cellular DNA after restriction endonuclease digestion and agarose gel electrophoresis. The plasmid was demonstrated by in situ hybridization to be present in large arrays integrated in metaphase chromosomes and in minute and double-minute replicating elements. In one subclone, approximately 60,000 copies of the plasmid were organized in a large array that resembles a chromosome, morphologically and in the segregation of its chromatids during anaphase. The original as well as modified versions of the plasmid were rescued by transformation of Escherichia coli using total cellular DNA. Southern blot analyses of recovered plasmids indicate the presence of mosquito-derived sequences. Images PMID:1631052</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26685998','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26685998"><span>Male meiosis in Crustacea: synapsis, recombination, epigenetics and fertility in Daphnia magna.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Gómez, Rocío; Van Damme, Kay; Gosálvez, Jaime; Morán, Eugenio Sánchez; Colbourne, John K</p>
<p>2016-09-01</p>
<p>We present the first detailed cytological study of male meiosis in Daphnia (Crustacea: Branchiopoda: Cladocera)-an aquatic microcrustacean with a cyclical parthenogenetic life cycle. Using immunostaining of the testes in Daphnia magna for baseline knowledge, we characterized the different stages of meiotic division and spermiogenesis in relation to the distribution of proteins involved in synapsis, early recombination events and sister chromatid cohesion. We also studied post-translational histone modifications in male spermatocytes, in relation to the dynamic chromatin progression of meiosis. Finally, we applied a DNA fragmentation test to measure sperm quality of D. magna, with respect to levels of inbreeding. As a proxy for fertility, this technique may be used to assess the reproductive health of a sentinel species of aquatic ecosystems. Daphnia proves to be a model species for comparative studies of meiosis that is poised to improve our understanding of the cytological basis of sexual and asexual reproduction.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/6396241-vitro-genotoxicity-chlorinated-drinking-water-processed-from-humus-rich-surface-water','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/6396241-vitro-genotoxicity-chlorinated-drinking-water-processed-from-humus-rich-surface-water"><span>In vitro genotoxicity of chlorinated drinking water processed from humus-rich surface water</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Liimatainen, A.; Grummt, T.</p>
<p></p>
<p>Chlorination by-products of drinking waters are capable of inducing sister chromatid exchanges (SCE) and chromosome aberrations (CA) in vitro, in addition to their mutagenic activity in the Ames test. Finnish drinking waters, processed from humus-rich surface water using chlorine disinfection, have been found to be highly mutagenic in the Ames' test. The highest activities have been found in the acidic, non-volatile fraction of the water concentrates using tester strain TA100 without metabolic activation by S9mix. The mutagenicities have varied between 500 and 14,000 induced revertants per liter. These figures are one to two magnitudes higher than those reported elsewhere. Themore » authors studied five Finnish drinking water samples for their potency to exert genotoxic effects, SCEs and CAs, in mammalian cells in vitro (human peripheral lymphocytes and Chinese hamster lung fibroblasts).« less</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/2047814','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/2047814"><span>Assessment of genotoxic exposure in Swedish coke-oven work by different methods of biological monitoring.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Reuterwall, C; Aringer, L; Elinder, C G; Rannug, A; Levin, J O; Juringe, L; Onfelt, A</p>
<p>1991-04-01</p>
<p>This study evaluated the results of several biological methods used simultaneously to monitor coke-oven work. Blood samples from 44 male coke-oven workers and 48 male referents, matched for age and smoking/snuff consumption, were examined for cytogenetic damage in lymphocytes. Urinary thioether excretion was determined for 62, and urine mutagenicity for 31, of the subjects, who followed a standardized diet during the urine sampling. Exposure to polycyclic aromatic hydrocarbons varied with work task, the ambient air levels of benzo[a]pyrene sometimes exceeding 5 micrograms/m3. Cytogenetic damage, urine mutagenicity, and thioether excretion did not differ between the groups. The smokers, however, had significantly higher sister chromatid exchange frequencies, urine mutagenicity, and thioether excretion than the nonsmokers. The absence of biological indications of genotoxic exposure was unexpected and indicates that the studied methods are not adequate to assess the carcinogenic risks of Swedish coke-oven workers.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/8684405','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/8684405"><span>In vitro studies on the genotoxicity of 2,4-dichloro-6-nitrophenol ammonium (DCNPA) and its major metabolite.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Heng, Z C; Ong, T; Nath, J</p>
<p>1996-06-12</p>
<p>2,4-dichloro-6-nitrophenol ammonium (DCNPA) is used as a herbicide. However, information on the potential health hazards of DCNPA is limited. In a previous study, we found that DCNPA is genotoxic to Bacillus subtilis and yeast. Further studies were performed to determine whether DCNPA and its major metabolite, 2,4-dichloro-6-aminophenol (DCAP), can induce reverse mutations in Salmonella, gene mutations at the HPRT locus, sister chromatid exchanges (SCEs) and micronuclei (MN) in V79 cells. Results show that DCNPA does not produce a positive response for any endpoint at concentrations tested. However, treatment of V79 cultures with DCAP caused a significant increase in SCEs and MN in a concentration-dependent manner. These results indicate that DCAP damages DNA and causes chromosomal aberrations in V79 cells. Therefore, DCNPA could pose potential health hazards to populations exposed to this herbicide.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/12616623','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/12616623"><span>Antigenotoxic potential of certain dietary constituents.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Shukla, Yogeshwer; Arora, Annu; Taneja, Pankaj</p>
<p>2003-01-01</p>
<p>The human diet contains a variety of compounds that exhibit chemopreventive effects towards an array of xenobiotics. In the present study, the antigenotoxic potential of selected dietary constituents including Diallyl sulfide (DAS), Indole-3-carbinol (I3C), Curcumin (CUR), and Black tea polyphenols (BTP) has been evaluated in the Salmonella typhimurium reverse mutation and mammalian in vivo cytogenetic assays. In addition, the anticlastogenic effect of the above dietary constituents was identified towards Benzo(a)pyrene (BaP) and cyclophosphamide- (CP) induced cytogenetic damage in mouse bone marrow cells. The induction of BaP and CP induced chromosomal aberrations, micronuclei formation, and sister chromatid exchanges (SCEs) were found to be inhibited in a dose-dependent manner by DAS, I3C, CUR, and BTP. Thus the study reveals the antimutagenic potential of these dietary compounds towards BaP- and CP-induced genotoxicity in microbial and mammalian test systems. Copyright 2003 Wiley-Liss, Inc.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27797077','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27797077"><span>Measuring Sister Chromatid Cohesion Protein Genome Occupancy in Drosophila melanogaster by ChIP-seq.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Dorsett, Dale; Misulovin, Ziva</p>
<p>2017-01-01</p>
<p>This chapter presents methods to conduct and analyze genome-wide chromatin immunoprecipitation of the cohesin complex and the Nipped-B cohesin loading factor in Drosophila cells using high-throughput DNA sequencing (ChIP-seq). Procedures for isolation of chromatin, immunoprecipitation, and construction of sequencing libraries for the Ion Torrent Proton high throughput sequencer are detailed, and computational methods to calculate occupancy as input-normalized fold-enrichment are described. The results obtained by ChIP-seq are compared to those obtained by ChIP-chip (genomic ChIP using tiling microarrays), and the effects of sequencing depth on the accuracy are analyzed. ChIP-seq provides similar sensitivity and reproducibility as ChIP-chip, and identifies the same broad regions of occupancy. The locations of enrichment peaks, however, can differ between ChIP-chip and ChIP-seq, and low sequencing depth can splinter broad regions of occupancy into distinct peaks.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4867242','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4867242"><span>Repression of harmful meiotic recombination in centromeric regions</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Nambiar, Mridula; Smith, Gerald R.</p>
<p>2016-01-01</p>
<p>During the first division of meiosis, segregation of homologous chromosomes reduces the chromosome number by half. In most species, sister chromatid cohesion and reciprocal recombination (crossing-over) between homologous chromosomes are essential to provide tension to signal proper chromosome segregation during the first meiotic division. Crossovers are not distributed uniformly throughout the genome and are repressed at and near the centromeres. Rare crossovers that occur too near or in the centromere interfere with proper segregation and can give rise to aneuploid progeny, which can be severely defective or inviable. We review here how crossing-over occurs and how it is prevented in and around the centromeres. Molecular mechanisms of centromeric repression are only now being elucidated. However, rapid advances in understanding crossing-over, chromosome structure, and centromere functions promise to explain how potentially deleterious crossovers are avoided in certain chromosomal regions while allowing beneficial crossovers in others. PMID:26849908</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/16481348','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/16481348"><span>Cytogenetic investigation of subjects professionally exposed to radiofrequency radiation.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Maes, Annemarie; Van Gorp, Urbain; Verschaeve, Luc</p>
<p>2006-03-01</p>
<p>Nowadays, virtually everybody is exposed to radiofrequency radiation (RFR) from mobile phone base station antennas or other sources. At least according to some scientists, this exposure can have detrimental health effects. We investigated cytogenetic effects in peripheral blood lymphocytes from subjects who were professionally exposed to mobile phone electromagnetic fields in an attempt to demonstrate possible RFR-induced genetic effects. These subjects can be considered well suited for this purpose as their RFR exposure is 'normal' though rather high, and definitely higher than that of the 'general population'. The alkaline comet assay, sister chromatid exchange (SCE) and chromosome aberration tests revealed no evidence of RFR-induced genetic effects. Blood cells were also exposed to the well known chemical mutagen mitomycin C in order to investigate possible combined effects of RFR and the chemical. No cooperative action was found between the electromagnetic field exposure and the mutagen using either the comet assay or SCE test.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26738809','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26738809"><span>Assessment of in vitro genotoxic and cytotoxic effects of flurbiprofen on human cultured lymphocytes.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Timocin, Taygun; Ila, Hasan Basri; Dordu, Tuba; Husunet, Mehmet Tahir; Tazehkand, Mostafa Norizadeh; Valipour, Ebrahim; Topaktas, Mehmet</p>
<p>2016-01-01</p>
<p>Flurbiprofen is non-steroidal anti-inflammatory drug which is commonly used for its analgesic, antipyretic, and anti-inflammatory effects. The purpose of the study was to explore the genotoxic and cytotoxic effects of flurbiprofen in human cultured lymphocytes by sister chromatid exchange, chromosome aberration, and cytokinesis-blocked micronucleus tests. 10, 20, 30, and 40 μg/mL concentrations of flurbiprofen (solvent is DMSO) were used to treatment of human cultured lymphocytes at two different treatment periods (24 and 48 h). Flurbiprofen had no significant genotoxic effect in any of these tests. But exposing to flurbiprofen for 24 and 48 h led to significant decrease on proliferation index, mitotic index, and nuclear division index (NDI). Also, all decreases were concentration-dependent (except NDI at 24 h treatment period). Consequently, the findings of this research showed that flurbiprofen had cytotoxic effects in human blood lymphocytes.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17586265','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17586265"><span>In situ analysis of DNA damage response and repair using laser microirradiation.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Kim, Jong-Soo; Heale, Jason T; Zeng, Weihua; Kong, Xiangduo; Krasieva, Tatiana B; Ball, Alexander R; Yokomori, Kyoko</p>
<p>2007-01-01</p>
<p>A proper response to DNA damage is critical for the maintenance of genome integrity. However, it is difficult to study the in vivo kinetics and factor requirements of the damage recognition process in mammalian cells. In order to address how the cell reacts to DNA damage, we utilized a second harmonic (532 nm) pulsed Nd:YAG laser to induce highly concentrated damage in a small area in interphase cell nuclei and cytologically analyzed both protein recruitment and modification. Our results revealed for the first time the sequential recruitment of factors involved in two major DNA double-strand break (DSB) repair pathways, non-homologous end-joining (NHEJ) and homologous recombination (HR), and the cell cycle-specific recruitment of the sister chromatid cohesion complex cohesin to the damage site. In this chapter, the strategy developed to study the DNA damage response using the 532-nm Nd:YAG laser will be summarized.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4937469','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4937469"><span>Chromosome Duplication in Saccharomyces cerevisiae</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Bell, Stephen P.; Labib, Karim</p>
<p>2016-01-01</p>
<p>The accurate and complete replication of genomic DNA is essential for all life. In eukaryotic cells, the assembly of the multi-enzyme replisomes that perform replication is divided into stages that occur at distinct phases of the cell cycle. Replicative DNA helicases are loaded around origins of DNA replication exclusively during G1 phase. The loaded helicases are then activated during S phase and associate with the replicative DNA polymerases and other accessory proteins. The function of the resulting replisomes is monitored by checkpoint proteins that protect arrested replisomes and inhibit new initiation when replication is inhibited. The replisome also coordinates nucleosome disassembly, assembly, and the establishment of sister chromatid cohesion. Finally, when two replisomes converge they are disassembled. Studies in Saccharomyces cerevisiae have led the way in our understanding of these processes. Here, we review our increasingly molecular understanding of these events and their regulation. PMID:27384026</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21782271','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21782271"><span>New and old ways to control meiotic recombination.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Phadnis, Naina; Hyppa, Randy W; Smith, Gerald R</p>
<p>2011-10-01</p>
<p>The unique segregation of homologs, rather than sister chromatids, at the first meiotic division requires the formation of crossovers (COs) between homologs by meiotic recombination in most species. Crossovers do not form at random along chromosomes. Rather, their formation is carefully controlled, both at the stage of formation of DNA double-strand breaks (DSBs) that can initiate COs and during the repair of these DSBs. Here, we review control of DSB formation and two recently recognized controls of DSB repair: CO homeostasis and CO invariance. Crossover homeostasis maintains a constant number of COs per cell when the total number of DSBs in a cell is experimentally or stochastically reduced. Crossover invariance maintains a constant CO density (COs per kb of DNA) across much of the genome despite strong DSB hotspots in some intervals. These recently uncovered phenomena show that CO control is even more complex than previously suspected. Copyright © 2011 Elsevier Ltd. All rights reserved.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20136045','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20136045"><span>Modulatory effects of garlic extract against the cyclophosphamide induced genotoxicity in human lymphocytes in vitro.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Sowjanya, B Lakshmi; Devi, K Rudrama; Madhavi, D</p>
<p>2009-09-01</p>
<p>Cyclophosphamide (CP) is a commonly used chemotherapeutic and immunosuppressive agent which is used in the treatment of wide range of cancers and autoimmune diseases. Besides that it is a well known carcinogen. In this study by using chromosomal aberrations (CA) and sister chromatid exchanges (SCE) assays method, the modulatory effects exerted by the extract of garlic against the CP induced genotoxicity in the human lymphocyte cultures in vitro were tested. Three different doses of garlic extract were tested for their modulatory capacity on the mutagenecity exerted by 100 microg ml(-1) of CR The results indicate a significant decrease in the frequency of CA and SCE suggesting that the garlic extract modulates the CP induced genotoxicity in a dose dependent manner. These findings provide the future directions for the research on design and development of possible modulatory drugs containing garlic extract.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5885250','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5885250"><span>Asymmetric spermatocyte division as a mechanism for controlling sex ratios</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Shakes, Diane C.; Neva, Bryan J.; Huynh, Henry; Chaudhuri, Jyotiska; Pires-daSilva, Andre</p>
<p>2016-01-01</p>
<p>Although Mendel's first law predicts that crosses between XY (or XO) males and XX females should yield equal numbers of males and females, individuals in a wide variety of metazoans transmit their sex chromosomes unequally and produce broods with highly skewed sex ratios. Here we report two modifications to the cellular program of spermatogenesis which, in combination, help explain why males of the free-living nematode species Rhabditis sp. SB347 sire less than 5% male progeny. First, the spermatogenesis program involves a modified meiosis in which chromatids of the unpaired X chromosome separate prematurely, in meiosis I. Second, during anaphase II, cellular components essential for sperm motility are partitioned almost exclusively to the X-bearing sperm. Our studies reveal a novel cellular mechanism for the differential transmission of X-bearing sperm and suggest R. sp. SB347 as a useful model for studying sex chromosome drive and the evolution of new mating systems. PMID:21245838</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21245838','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21245838"><span>Asymmetric spermatocyte division as a mechanism for controlling sex ratios.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Shakes, Diane C; Neva, Bryan J; Huynh, Henry; Chaudhuri, Jyotiska; Pires-Dasilva, Andre</p>
<p>2011-01-18</p>
<p>Although Mendel's first law predicts that crosses between XY (or XO) males and XX females should yield equal numbers of males and females, individuals in a wide variety of metazoans transmit their sex chromosomes unequally and produce broods with highly skewed sex ratios. Here, we report two modifications to the cellular programme of spermatogenesis, which, in combination, help to explain why males of the free-living nematode species Rhabditis sp. SB347 sire <5% male progeny. First, the spermatogenesis programme involves a modified meiosis in which chromatids of the unpaired X chromosome separate prematurely, in meiosis I. Second, during anaphase II, cellular components essential for sperm motility are partitioned almost exclusively to the X-bearing sperm. Our studies reveal a novel cellular mechanism for the differential transmission of X-bearing sperm and suggest Rhabditis sp. SB347 as a useful model for studying sex chromosome drive and the evolution of new mating systems.</p>
</li>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22869596','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22869596"><span>Kinase-dead ATM protein causes genomic instability and early embryonic lethality in mice.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Yamamoto, Kenta; Wang, Yunyue; Jiang, Wenxia; Liu, Xiangyu; Dubois, Richard L; Lin, Chyuan-Sheng; Ludwig, Thomas; Bakkenist, Christopher J; Zha, Shan</p>
<p>2012-08-06</p>
<p>Ataxia telangiectasia (A-T) mutated (ATM) kinase orchestrates deoxyribonucleic acid (DNA) damage responses by phosphorylating numerous substrates implicated in DNA repair and cell cycle checkpoint activation. A-T patients and mouse models that express no ATM protein undergo normal embryonic development but exhibit pleiotropic DNA repair defects. In this paper, we report that mice carrying homozygous kinase-dead mutations in Atm (Atm(KD/KD)) died during early embryonic development. Atm(KD/-) cells exhibited proliferation defects and genomic instability, especially chromatid breaks, at levels higher than Atm(-/-) cells. Despite this increased genomic instability, Atm(KD/-) lymphocytes progressed through variable, diversity, and joining recombination and immunoglobulin class switch recombination, two events requiring nonhomologous end joining, at levels comparable to Atm(-/-) lymphocytes. Together, these results reveal an essential function of ATM during embryogenesis and an important function of catalytically inactive ATM protein in DNA repair.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23022599','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23022599"><span>Genetic damage in human cells exposed to non-ionizing radiofrequency fields: a meta-analysis of the data from 88 publications (1990-2011).</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Vijayalaxmi; Prihoda, Thomas J</p>
<p>2012-12-12</p>
<p>Based on the 'limited' evidence suggesting an association between exposure to radiofrequency fields (RF) emitted from mobile phones and two types of brain cancer, glioma and acoustic neuroma, the International Agency for Research on Cancer has classified RF as 'possibly carcinogenic to humans' in group 2B. In view of this classification and the positive correlation between increased genetic damage and carcinogenesis, a meta-analysis was conducted to determine whether a significant increase in genetic damage in human cells exposed to RF provides a potential mechanism for its carcinogenic potential. The extent of genetic damage in human cells, assessed from various end-points, viz., single-/double-strand breaks in the DNA, incidence of chromosomal aberrations, micronuclei and sister chromatid exchanges, reported in a total of 88 peer-reviewed scientific publications during 1990-2011 was considered in the meta-analysis. Among the several variables in the experimental protocols used, the influence of five specific variables related to RF exposure characteristics was investigated: (i) frequency, (ii) specific absorption rate, (iii) exposure as continuous wave, pulsed wave and occupationally exposed/mobile phone users, (iv) duration of exposure, and (v) different cell types. The data indicated the following. (1) The magnitude of difference between RF-exposed and sham-/un-exposed controls was small with some exceptions. (2) In certain RF exposure conditions there was a statistically significant increase in genotoxicity assessed from some end-points: the effect was observed in studies with small sample size and was largely influenced by publication bias. Studies conducted within the generally recommended RF exposure guidelines showed a smaller effect. (3) The multiple regression analyses and heterogeneity goodness of fit data indicated that factors other than the above five variables as well as the quality of publications have contributed to the overall results. (4) More importantly, the mean indices for chromosomal aberrations, micronuclei and sister chromatid exchange end-points in RF-exposed and sham-/un-exposed controls were within the spontaneous levels reported in a large data-base. Thus, the classification of RF as possibly carcinogenic to humans in group 2B was not supported by genotoxicity-based mechanistic evidence. Copyright © 2012 Elsevier B.V. All rights reserved.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4081007','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4081007"><span>Meiosis-Specific Cohesin Component, Stag3 Is Essential for Maintaining Centromere Chromatid Cohesion, and Required for DNA Repair and Synapsis between Homologous Chromosomes</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Hopkins, Jessica; Bedigian, Rick; Oka, Kazuhiro; Overbeek, Paul; Murray, Steve; Jordan, Philip W.</p>
<p>2014-01-01</p>
<p>Cohesins are important for chromosome structure and chromosome segregation during mitosis and meiosis. Cohesins are composed of two structural maintenance of chromosomes (SMC1-SMC3) proteins that form a V-shaped heterodimer structure, which is bridged by a α-kleisin protein and a stromal antigen (STAG) protein. Previous studies in mouse have shown that there is one SMC1 protein (SMC1β), two α-kleisins (RAD21L and REC8) and one STAG protein (STAG3) that are meiosis-specific. During meiosis, homologous chromosomes must recombine with one another in the context of a tripartite structure known as the synaptonemal complex (SC). From interaction studies, it has been shown that there are at least four meiosis-specific forms of cohesin, which together with the mitotic cohesin complex, are lateral components of the SC. STAG3 is the only meiosis-specific subunit that is represented within all four meiosis-specific cohesin complexes. In Stag3 mutant germ cells, the protein level of other meiosis-specific cohesin subunits (SMC1β, RAD21L and REC8) is reduced, and their localization to chromosome axes is disrupted. In contrast, the mitotic cohesin complex remains intact and localizes robustly to the meiotic chromosome axes. The instability of meiosis-specific cohesins observed in Stag3 mutants results in aberrant DNA repair processes, and disruption of synapsis between homologous chromosomes. Furthermore, mutation of Stag3 results in perturbation of pericentromeric heterochromatin clustering, and disruption of centromere cohesion between sister chromatids during meiotic prophase. These defects result in early prophase I arrest and apoptosis in both male and female germ cells. The meiotic defects observed in Stag3 mutants are more severe when compared to single mutants for Smc1β, Rec8 and Rad21l, however they are not as severe as the Rec8, Rad21l double mutants. Taken together, our study demonstrates that STAG3 is required for the stability of all meiosis-specific cohesin complexes. Furthermore, our data suggests that STAG3 is required for structural changes of chromosomes that mediate chromosome pairing and synapsis, DNA repair and progression of meiosis. PMID:24992337</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24992337','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24992337"><span>Meiosis-specific cohesin component, Stag3 is essential for maintaining centromere chromatid cohesion, and required for DNA repair and synapsis between homologous chromosomes.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Hopkins, Jessica; Hwang, Grace; Jacob, Justin; Sapp, Nicklas; Bedigian, Rick; Oka, Kazuhiro; Overbeek, Paul; Murray, Steve; Jordan, Philip W</p>
<p>2014-07-01</p>
<p>Cohesins are important for chromosome structure and chromosome segregation during mitosis and meiosis. Cohesins are composed of two structural maintenance of chromosomes (SMC1-SMC3) proteins that form a V-shaped heterodimer structure, which is bridged by a α-kleisin protein and a stromal antigen (STAG) protein. Previous studies in mouse have shown that there is one SMC1 protein (SMC1β), two α-kleisins (RAD21L and REC8) and one STAG protein (STAG3) that are meiosis-specific. During meiosis, homologous chromosomes must recombine with one another in the context of a tripartite structure known as the synaptonemal complex (SC). From interaction studies, it has been shown that there are at least four meiosis-specific forms of cohesin, which together with the mitotic cohesin complex, are lateral components of the SC. STAG3 is the only meiosis-specific subunit that is represented within all four meiosis-specific cohesin complexes. In Stag3 mutant germ cells, the protein level of other meiosis-specific cohesin subunits (SMC1β, RAD21L and REC8) is reduced, and their localization to chromosome axes is disrupted. In contrast, the mitotic cohesin complex remains intact and localizes robustly to the meiotic chromosome axes. The instability of meiosis-specific cohesins observed in Stag3 mutants results in aberrant DNA repair processes, and disruption of synapsis between homologous chromosomes. Furthermore, mutation of Stag3 results in perturbation of pericentromeric heterochromatin clustering, and disruption of centromere cohesion between sister chromatids during meiotic prophase. These defects result in early prophase I arrest and apoptosis in both male and female germ cells. The meiotic defects observed in Stag3 mutants are more severe when compared to single mutants for Smc1β, Rec8 and Rad21l, however they are not as severe as the Rec8, Rad21l double mutants. Taken together, our study demonstrates that STAG3 is required for the stability of all meiosis-specific cohesin complexes. Furthermore, our data suggests that STAG3 is required for structural changes of chromosomes that mediate chromosome pairing and synapsis, DNA repair and progression of meiosis.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22041523','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22041523"><span>Assessment in vitro of cytogenetic and genotoxic effects of propolis on human lymphocytes.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Montoro, A; Soriano, J M; Barquinero, J F; Almonacid, M; Montoro, A; Verdú, G; Sahuquillo, V; Villaescusa, J I; Sebastià, N</p>
<p>2012-02-01</p>
<p>We evaluated the genetic damage by ethanolic extract of propolis (EEP) induced to human lymphocytes which were exposed to increasing concentrations (0-2000μgml(-1)). The results indicated that EEP reduced significantly the mitotic index (MI) and proliferation index (PI) when high concentrations of EEP were used. Sister chromatid exchange (SCE) rates indicated that EEP could have genotoxic effects at high concentrations. Exposure of the cells to the amount of ethanol used as solvent did not alter either the MI and cell proliferation kinetics (CPK), or the rate of SCE. The results showed: (a) statistical increase in the percentage the cells with CAs and in the frequency of SCE at the highest concentrations, (b) a decrease in MI and in the CPK values was observed, (c) no effect was noticed in negative controls. In conclusion, it can be assumed that high concentrations of EEP have a cyto and genotoxic effect, in vitro, for human peripheral lymphocytes. Copyright © 2011 Elsevier Ltd. All rights reserved.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5331533','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5331533"><span>Evidence of Some Natural Products with Antigenotoxic Effects. Part 1: Fruits and Polysaccharides</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Izquierdo-Vega, Jeannett Alejandra; Morales-González, José Antonio; Sánchez-Gutiérrez, Manuel; Betanzos-Cabrera, Gabriel; Sosa-Delgado, Sara M.; Sumaya-Martínez, María Teresa; Morales-González, Ángel; Paniagua-Pérez, Rogelio; Madrigal-Bujaidar, Eduardo; Madrigal-Santillán, Eduardo</p>
<p>2017-01-01</p>
<p>Cancer is one of the leading causes of deaths worldwide. The agents capable of causing damage to genetic material are known as genotoxins and, according to their mode of action, are classified into mutagens, carcinogens or teratogens. Genotoxins are involved in the pathogenesis of several chronic degenerative diseases including hepatic, neurodegenerative and cardiovascular disorders, diabetes, arthritis, cancer, chronic inflammation and ageing. In recent decades, researchers have found novel bioactive phytocompounds able to counteract the effects of physical and chemical mutagens. Several studies have shown potential antigenotoxicity in a variety of fruits. In this review (Part 1), we present an overview of research conducted on some fruits (grapefruit, cranberries, pomegranate, guava, pineapple, and mango) which are frequently consumed by humans, as well as the analysis of some phytochemicals extracted from fruits and yeasts which have demonstrated antigenotoxic capacity in various tests, including the Ames assay, sister chromatid exchange, chromosomal aberrations, micronucleus and comet assay. PMID:28157162</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27487930','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27487930"><span>Characterization of the NTPR and BD1 interacting domains of the human PICH-BEND3 complex.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Pitchai, Ganesha P; Hickson, Ian D; Streicher, Werner; Montoya, Guillermo; Mesa, Pablo</p>
<p>2016-08-01</p>
<p>Chromosome integrity depends on DNA structure-specific processing complexes that resolve DNA entanglement between sister chromatids. If left unresolved, these entanglements can generate either chromatin bridging or ultrafine DNA bridging in the anaphase of mitosis. These bridge structures are defined by the presence of the PICH protein, which interacts with the BEND3 protein in mitosis. To obtain structural insights into PICH-BEND3 complex formation at the atomic level, their respective NTPR and BD1 domains were cloned, overexpressed and crystallized using 1.56 M ammonium sulfate as a precipitant at pH 7.0. The protein complex readily formed large hexagonal crystals belonging to space group P6122, with unit-cell parameters a = b = 47.28, c = 431.58 Å and with one heterodimer in the asymmetric unit. A complete multiwavelength anomalous dispersion (MAD) data set extending to 2.2 Å resolution was collected from a selenomethionine-labelled crystal at the Swiss Light Source.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4344887','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4344887"><span>DNA sequence alignment by microhomology sampling during homologous recombination</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Qi, Zhi; Redding, Sy; Lee, Ja Yil; Gibb, Bryan; Kwon, YoungHo; Niu, Hengyao; Gaines, William A.; Sung, Patrick</p>
<p>2015-01-01</p>
<p>Summary Homologous recombination (HR) mediates the exchange of genetic information between sister or homologous chromatids. During HR, members of the RecA/Rad51 family of recombinases must somehow search through vast quantities of DNA sequence to align and pair ssDNA with a homologous dsDNA template. Here we use single-molecule imaging to visualize Rad51 as it aligns and pairs homologous DNA sequences in real-time. We show that Rad51 uses a length-based recognition mechanism while interrogating dsDNA, enabling robust kinetic selection of 8-nucleotide (nt) tracts of microhomology, which kinetically confines the search to sites with a high probability of being a homologous target. Successful pairing with a 9th nucleotide coincides with an additional reduction in binding free energy and subsequent strand exchange occurs in precise 3-nt steps, reflecting the base triplet organization of the presynaptic complex. These findings provide crucial new insights into the physical and evolutionary underpinnings of DNA recombination. PMID:25684365</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26620470','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26620470"><span>Stable kinetochore-microtubule attachment is sufficient to silence the spindle assembly checkpoint in human cells.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Tauchman, Eric C; Boehm, Frederick J; DeLuca, Jennifer G</p>
<p>2015-12-01</p>
<p>During mitosis, duplicated sister chromatids attach to microtubules emanating from opposing sides of the bipolar spindle through large protein complexes called kinetochores. In the absence of stable kinetochore-microtubule attachments, a cell surveillance mechanism known as the spindle assembly checkpoint (SAC) produces an inhibitory signal that prevents anaphase onset. Precisely how the inhibitory SAC signal is extinguished in response to microtubule attachment remains unresolved. To address this, we induced formation of hyper-stable kinetochore-microtubule attachments in human cells using a non-phosphorylatable version of the protein Hec1, a core component of the attachment machinery. We find that stable attachments are sufficient to silence the SAC in the absence of sister kinetochore bi-orientation and strikingly in the absence of detectable microtubule pulling forces or tension. Furthermore, we find that SAC satisfaction occurs despite the absence of large changes in intra-kinetochore distance, suggesting that substantial kinetochore stretching is not required for quenching the SAC signal.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28930671','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28930671"><span>Cohesin Can Remain Associated with Chromosomes during DNA Replication.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Rhodes, James D P; Haarhuis, Judith H I; Grimm, Jonathan B; Rowland, Benjamin D; Lavis, Luke D; Nasmyth, Kim A</p>
<p>2017-09-19</p>
<p>To ensure disjunction to opposite poles during anaphase, sister chromatids must be held together following DNA replication. This is mediated by cohesin, which is thought to entrap sister DNAs inside a tripartite ring composed of its Smc and kleisin (Scc1) subunits. How such structures are created during S phase is poorly understood, in particular whether they are derived from complexes that had entrapped DNAs prior to replication. To address this, we used selective photobleaching to determine whether cohesin associated with chromatin in G1 persists in situ after replication. We developed a non-fluorescent HaloTag ligand to discriminate the fluorescence recovery signal from labeling of newly synthesized Halo-tagged Scc1 protein (pulse-chase or pcFRAP). In cells where cohesin turnover is inactivated by deletion of WAPL, Scc1 can remain associated with chromatin throughout S phase. These findings suggest that cohesion might be generated by cohesin that is already bound to un-replicated DNA. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/10505272','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/10505272"><span>[Unusually high level of chromosome variability in cultured human peripheral blood lymphocytes].</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Bochkov, N P; Popova, N A; Katosova, L D; Iakovleva, Iu S; Nazarenko, S A; Vasil'eva, E O; Platonova, V I; Chebotarev, A N</p>
<p>1999-06-01</p>
<p>A cytogenetic examination carried out in the inhabitants of Seversk (Tomsk oblast) and workers of the Siberian chemical industrial complex (a complex of nuclear-chemical and fuel plants), living in the same town, revealed unusually high level of spontaneous chromosomal variability both in control and industrial groups (total irradiation doses 1.8 to 3.7 and 9.3 to 15.7 Gy, respectively). The frequencies of cells with chromosomal aberrations (estimated per 100 cells) in control and industrial groups were 4.69, 6.04, and 6.64, respectively, and the total number of aberrations constituted 6.93, 8.47 and 12.06, respectively. These frequencies were several times higher compared to the summarized literature data on the control levels. The high average aberration level was caused by the elevated proportion of chromatid-type aberrations and paired fragments. The reasons for this are unclear. The levels of radioactive background and chemical air pollution in the town were not increased.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/18995837','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/18995837"><span>Structure and substrate recruitment of the human spindle checkpoint kinase Bub1.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Kang, Jungseog; Yang, Maojun; Li, Bing; Qi, Wei; Zhang, Chao; Shokat, Kevan M; Tomchick, Diana R; Machius, Mischa; Yu, Hongtao</p>
<p>2008-11-07</p>
<p>In mitosis, the spindle checkpoint detects a single unattached kinetochore, inhibits the anaphase-promoting complex or cyclosome (APC/C), and prevents premature sister chromatid separation. The checkpoint kinase Bub1 contributes to checkpoint sensitivity through phosphorylating the APC/C activator, Cdc20, and inhibiting APC/C catalytically. We report here the crystal structure of the kinase domain of Bub1, revealing the requirement of an N-terminal extension for its kinase activity. Though the activation segment of Bub1 is ordered and has structural features indicative of active kinases, the C-terminal portion of this segment sterically restricts substrate access to the active site. Bub1 uses docking motifs, so-called KEN boxes, outside its kinase domain to recruit Cdc20, one of two known KEN box receptors. The KEN boxes of Bub1 are required for the spindle checkpoint in human cells. Therefore, its unusual active-site conformation and mode of substrate recruitment suggest that Bub1 has an exquisitely tuned specificity for Cdc20.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21130826','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21130826"><span>The evaluation of the genotoxicity of two food preservatives: sodium benzoate and potassium benzoate.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Zengin, N; Yüzbaşıoğlu, D; Unal, F; Yılmaz, S; Aksoy, H</p>
<p>2011-04-01</p>
<p>In this study, the genotoxic effects of sodium benzoate (SB) and potassium benzoate (PB) were investigated in cultured human peripheral lymphocytes using chromosomal aberrations (CA), sister chromatid exchange (SCE), and micronuclei (MN). The level of nuclear DNA damage of SB and PB were also evaluated using the comet assay. The lymphocytes were incubated with different concentrations of SB (6.25, 12.5, 25, 50, and 100 μg/ml) and PB (62.5, 125, 250, 500, and 1000 μg/ml). A significant increase was observed in CA, SCE, and MN, in almost all treatments compared to negative controls. SB and PB significantly decreased the mitotic index (MI) in all the treatments, compared to the negative controls. However, neither of the additives affected the replication index (RI). Although SB significantly increased DNA damage, PB did not cause a significant increase in DNA damage. The present results indicate that SB and PB are clastogenic, mutagenic and cytotoxic to human lymphocytes in vitro. Copyright © 2010 Elsevier Ltd. All rights reserved.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4142609','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4142609"><span>ROCC, a conserved region in cohesin's Mcd1 subunit, is essential for the proper regulation of the maintenance of cohesion and establishment of condensation</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Eng, Thomas; Guacci, Vincent; Koshland, Doug</p>
<p>2014-01-01</p>
<p>Cohesin helps orchestrate higher-order chromosome structure, thereby promoting sister chromatid cohesion, chromosome condensation, DNA repair, and transcriptional regulation. To elucidate how cohesin facilitates these diverse processes, we mutagenized Mcd1p, the kleisin regulatory subunit of budding yeast cohesin. In the linker region of Mcd1p, we identified a novel evolutionarily conserved 10–amino acid cluster, termed the regulation of cohesion and condensation (ROCC) box. We show that ROCC promotes cohesion maintenance by protecting a second activity of cohesin that is distinct from its stable binding to chromosomes. The existence of this second activity is incompatible with the simple embrace mechanism of cohesion. In addition, we show that the ROCC box is required for the establishment of condensation. We provide evidence that ROCC controls cohesion maintenance and condensation establishment through differential functional interactions with Pds5p and Wpl1p. PMID:24966169</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3761645','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3761645"><span>Polo kinase Cdc5 is a central regulator of meiosis I</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Attner, Michelle A.; Miller, Matthew P.; Ee, Ly-sha; Elkin, Sheryl K.; Amon, Angelika</p>
<p>2013-01-01</p>
<p>During meiosis, two consecutive rounds of chromosome segregation yield four haploid gametes from one diploid cell. The Polo kinase Cdc5 is required for meiotic progression, but how Cdc5 coordinates multiple cell-cycle events during meiosis I is not understood. Here we show that CDC5-dependent phosphorylation of Rec8, a subunit of the cohesin complex that links sister chromatids, is required for efficient cohesin removal from chromosome arms, which is a prerequisite for meiosis I chromosome segregation. CDC5 also establishes conditions for centromeric cohesin removal during meiosis II by promoting the degradation of Spo13, a protein that protects centromeric cohesin during meiosis I. Despite CDC5’s central role in meiosis I, the protein kinase is dispensable during meiosis II and does not even phosphorylate its meiosis I targets during the second meiotic division. We conclude that Cdc5 has evolved into a master regulator of the unique meiosis I chromosome segregation pattern. PMID:23918381</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=15018','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=15018"><span>Role for the Silencing Protein Dot1 in Meiotic Checkpoint Control</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>San-Segundo, Pedro A.; Roeder, G. Shirleen</p>
<p>2000-01-01</p>
<p>During the meiotic cell cycle, a surveillance mechanism called the “pachytene checkpoint” ensures proper chromosome segregation by preventing meiotic progression when recombination and chromosome synapsis are defective. The silencing protein Dot1 (also known as Pch1) is required for checkpoint-mediated pachytene arrest of the zip1 and dmc1 mutants of Saccharomyces cerevisiae. In the absence of DOT1, the zip1 and dmc1 mutants inappropriately progress through meiosis, generating inviable meiotic products. Other components of the pachytene checkpoint include the nucleolar protein Pch2 and the heterochromatin component Sir2. In dot1, disruption of the checkpoint correlates with the loss of concentration of Pch2 and Sir2 in the nucleolus. In addition to its checkpoint function, Dot1 blocks the repair of meiotic double-strand breaks by a Rad54-dependent pathway of recombination between sister chromatids. In vegetative cells, mutation of DOT1 results in delocalization of Sir3 from telomeres, accounting for the impaired telomeric silencing in dot1. PMID:11029058</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5130098','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5130098"><span>A Regulatory Switch Alters Chromosome Motions at the Metaphase to Anaphase Transition</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Su, Kuan-Chung; Barry, Zachary; Schweizer, Nina; Maiato, Helder; Bathe, Mark; Cheeseman, Iain McPherson</p>
<p>2016-01-01</p>
<p>Summary To achieve chromosome segregation during mitosis, sister chromatids must undergo a dramatic change in their behavior to switch from balanced oscillations at the metaphase plate to directed poleward motion during anaphase. However, the factors that alter chromosome behavior at the metaphase-to-anaphase transition remain incompletely understood. Here, we perform time-lapse imaging to analyze anaphase chromosome dynamics in human cells. Using multiple directed biochemical, genetic, and physical perturbations, our results demonstrate that differences in the global phosphorylation states between metaphase and anaphase are the major determinant of chromosome motion dynamics. Indeed, causing a mitotic phosphorylation state to persist into anaphase produces dramatic metaphase-like oscillations. These induced oscillations depend on both kinetochore-derived and polar ejection forces that oppose poleward motion. Thus, our analysis of anaphase chromosome motion reveals that dephosphorylation of multiple mitotic substrates is required to suppress metaphase chromosome oscillatory motions and achieve directed poleward motion for successful chromosome segregation. PMID:27829144</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20306325','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20306325"><span>The perpetual movements of anaphase.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Maiato, Helder; Lince-Faria, Mariana</p>
<p>2010-07-01</p>
<p>One of the most extraordinary events in the lifetime of a cell is the coordinated separation of sister chromatids during cell division. This is truly the essence of the entire mitotic process and the reason for the most profound morphological changes in cytoskeleton and nuclear organization that a cell may ever experience. It all occurs within a very short time window known as "anaphase", as if the cell had spent the rest of its existence getting ready for this moment in an ultimate act of survival. And there is a good reason for this: no space for mistakes. Problems in the distribution of chromosomes during cell division have been correlated with aneuploidy, a common feature observed in cancers and several birth defects, and the main cause of spontaneous abortion in humans. In this paper, we critically review the mechanisms of anaphase chromosome motion that resisted the scrutiny of more than 100 years of research, as part of a tribute to the pioneering work of Miguel Mota.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/86423-sodium-arsenite-induces-chromosome-endoreduplication-inhibits-protein-phosphatase-activity-human-fibroblasts','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/86423-sodium-arsenite-induces-chromosome-endoreduplication-inhibits-protein-phosphatase-activity-human-fibroblasts"><span>Sodium arsenite induces chromosome endoreduplication and inhibits protein phosphatase activity in human fibroblasts</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Rong-Nan Huang; I-Ching Ho; Ling-Hui Yih</p>
<p></p>
<p>Arsenic, strongly associated with increased risks of human cancers, is a potent clastogen in a variety of mammalian cell systems. The effect of sodium arsenite (a trivalent arsenic compound) on chromatid separation was studied in human skin fibroblasts (HFW). Human fibroblasts were arrested in S phase by the aid of serum starvation and aphidicolin blocking and then these cells were allowed to synchronously progress into G2 phase. Treatment of the G2-enriched HFW cells with sodium arsenite (0-200 {mu}M) resulted in arrest of cells in the G2 phase, interference with mitotic division, inhibition of spindle assembly, and induction of chromosome endoreduplicationmore » in their second mitosis. Sodium arsenite treatment also inhibited the activities of serine/threonine protein phosphatases and enhanced phosphorylation levels of a small heat shock protein (HSP27). These results suggest that sodium arsenite may mimic okadaic acid to induce chromosome endoreduplication through its inhibitory effect on protein phosphatase activity. 61 refs., 6 figs., 2 tabs.« less</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24801345','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24801345"><span>Centromeres and kinetochores of Brassicaceae.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Lermontova, Inna; Sandmann, Michael; Demidov, Dmitri</p>
<p>2014-06-01</p>
<p>The centromere-the primary constriction of monocentric chromosomes-is essential for correct segregation of chromosomes during mitosis and meiosis. Centromeric DNA varies between different organisms in sequence composition and extension. The main components of centromeric and pericentromeric DNA of Brassicaceae species are centromeric satellite repeats. Centromeric DNA initiates assembly of the kinetochore, the large protein complex where the spindle fibers attach during nuclear division to pull sister chromatids apart. Kinetochore assembly is initiated by incorporation of the centromeric histone H3 cenH3 into centromeric nucleosomes. The spindle assembly checkpoint acts during mitosis and meiosis at centromeres and maintains genome stability by preventing chromosome segregation before all kinetochores are correctly attached to microtubules. The function of the spindle assembly checkpoint in plants is still poorly understood. Here, we review recent advances of studies on structure and functional importance of centromeric DNA of Brassicaceae, assembly and function of cenH3 in Arabidopsis thaliana and characterization of core SAC proteins of A. thaliana in comparison with non-plant homologues.</p>
</li>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4254552','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4254552"><span>The chromosome axis controls meiotic events through a hierarchical assembly of HORMA domain proteins</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Kim, Yumi; Rosenberg, Scott C.; Kugel, Christine L.; Kostow, Nora; Rog, Ofer; Davydov, Vitaliy; Su, Tiffany Y.; Dernburg, Abby F.; Corbett, Kevin D.</p>
<p>2014-01-01</p>
<p>Summary Proteins of the HORMA domain family play central but poorly understood roles in chromosome organization and dynamics during meiosis. In C. elegans, four such proteins (HIM-3, HTP-1, HTP-2, and HTP-3) have distinct but overlapping functions. Through combined biochemical, structural, and in vivo analysis, we find that these proteins form hierarchical complexes through binding of their HORMA domains to cognate peptides within their partners’ C-terminal tails, analogous to the “safety belt” binding mechanism of Mad2. These interactions are critical for recruitment of HIM-3, HTP-1, and HTP-2 to chromosome axes. HTP-3, in addition to recruiting the other HORMA domain proteins to the axis, plays an independent role in sister chromatid cohesion and double-strand break formation. Finally, we find that mammalian HORMAD1 binds a peptide motif found both at its own C-terminus and that of HORMAD2, indicating that this mode of intermolecular association is a conserved feature of meiotic chromosome structure in eukaryotes. PMID:25446517</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2640231','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2640231"><span>Architecture and Flexibility of the Yeast Ndc80 Kinetochore Complex</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Wang, Hong-Wei; Long, Sydney; Ciferri, Claudio; Westermann, Stefan; Drubin, David; Barnes, Georjana; Nogales, Eva</p>
<p>2008-01-01</p>
<p>Kinetochores mediate microtubule–chromosome attachment and ensure accurate segregation of sister chromatids. The highly conserved Ndc80 kinetochore complex makes direct contacts with the microtubule and is essential for spindle checkpoint signaling. It contains a long coiled-coil region with globular domains at each end involved in kinetochore localization and microtubule binding, respectively. We have directly visualized the architecture of the yeast Ndc80 complex and found a dramatic kink within the 560-Å coiled-coil rod located about 160 Å from the larger globular head. Comparison of our electron microscopy images to the structure of the human Ndc80 complex allowed us to position the kink proximal to the microtubule-binding end and to define the conformational range of the complex. The position of the kink coincides with a coiled-coil breaking region conserved across eukaryotes. We hypothesize that the kink in Ndc80 is essential for correct kinetochore geometry and could be part of a tension-sensing mechanism at the kinetochore. PMID:18793650</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2193093','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2193093"><span>Short Telomeres Result in Organismal Hypersensitivity to Ionizing Radiation in Mammals</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Goytisolo, Fermín A.; Samper, Enrique; Martín-Caballero, Juan; Finnon, Paul; Herrera, Eloísa; Flores, Juana M.; Bouffler, Simon D.; Blasco, María A.</p>
<p>2000-01-01</p>
<p>Here we show a correlation between telomere length and organismal sensitivity to ionizing radiation (IR) in mammals. In particular, fifth generation (G5) mouse telomerase RNA (mTR)−/− mice, with telomeres 40% shorter than in wild-type mice, are hypersensitive to cumulative doses of gamma rays. 60% of the irradiated G5 mTR−/− mice die of acute radiation toxicity in the gastrointestinal tract, lymphoid organs, and kidney. The affected G5 mTR−/− mice show higher chromosomal damage and greater apoptosis than similarly irradiated wild-type controls. Furthermore, we show that G5 mTR−/− mice show normal frequencies of sister chromatid exchange and normal V(D)J recombination, suggesting that short telomeres do not significantly affect the efficiency of DNA double strand break repair in mammals. The IR-sensitive phenotype of G5 mTR−/− mice suggests that telomere function is one of the determinants of radiation sensitivity of whole animals. PMID:11104804</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3525924','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3525924"><span>Meiosis I chromosome segregation is established through regulation of microtubule–kinetochore interactions</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Miller, Matthew P; Ünal, Elçin; Brar, Gloria A; Amon, Angelika</p>
<p>2012-01-01</p>
<p>During meiosis, a single round of DNA replication is followed by two consecutive rounds of nuclear divisions called meiosis I and meiosis II. In meiosis I, homologous chromosomes segregate, while sister chromatids remain together. Determining how this unusual chromosome segregation behavior is established is central to understanding germ cell development. Here we show that preventing microtubule–kinetochore interactions during premeiotic S phase and prophase I is essential for establishing the meiosis I chromosome segregation pattern. Premature interactions of kinetochores with microtubules transform meiosis I into a mitosis-like division by disrupting two key meiosis I events: coorientation of sister kinetochores and protection of centromeric cohesin removal from chromosomes. Furthermore we find that restricting outer kinetochore assembly contributes to preventing premature engagement of microtubules with kinetochores. We propose that inhibition of microtubule–kinetochore interactions during premeiotic S phase and prophase I is central to establishing the unique meiosis I chromosome segregation pattern. DOI: http://dx.doi.org/10.7554/eLife.00117.001 PMID:23275833</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1016386','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1016386"><span>ICF syndrome with variable expression in sibs.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Gimelli, G; Varone, P; Pezzolo, A; Lerone, M; Pistoia, V</p>
<p>1993-01-01</p>
<p>We describe a new familial case of ICF syndrome (immunodeficiency, centromeric instability, facial anomalies) in a woman of 29 years and in her brother of 30 years. The proband showed mental retardation, facial anomalies, recurrent respiratory infections, combined deficit of IgM and IgE immunoglobulin classes, and paracentromeric heterochromatin instability of chromosomes 1, 9, and 16. The brother had minor signs of the syndrome and had an apparently normal phenotype. Their parents were healthy and non-consanguineous. Chromosome anomalies consisted of homologous and non-homologous associations, chromatid and isochromatid breaks, deletions of whole arms, interchanges in the paracentromeric region, and multibranched configurations of chromosomes 1, 9, and 16. CD bands and fluorescence in situ hybridisation with alphoid DNA sequence probes specific for the centromeres of chromosomes 1 and 16 showed that the centromere was not directly implicated in the formation of multibranched configurations. These cases indicate the autosomal recessive mode of inheritance and the variable expressivity of the ICF syndrome. Images PMID:8320711</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23482750','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23482750"><span>Increased alternative lengthening of telomere phenotypes of telomerase-negative immortal cells upon trichostatin--a treatment.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Jung, A Ra; Yoo, Jeong Eun; Shim, Yhong-Hee; Choi, Ye-Na; Jeung, Hei-Cheul; Chung, Hyun Cheol; Rha, Sun Young; Oh, Bong-Kyeong</p>
<p>2013-03-01</p>
<p>Human immortal cells maintain their telomeres either by telomerase or by alternative lengthening of telomeres (ALT) that is based on homologous telomeric recombination. Previous studies showed that the ALT mechanism is activated in non-ALT cells when heterochromatic features are reduced. In this study, we examined the ALT phenotypes of ALT cells after treatment with trichostatin-A (TSA), which is an inhibitor of histone deacetylases and causes global chromatin decondensation. The ALT cells remained telomerase-negative after TSA treatment. ALT-associated promyelocytic leukemia (PML) nuclear bodies and telomere sister chromatid exchanges, typical ALT phenotypes, markedly increased in the TSA-treated cells, while the telomere length remained unchanged. In addition, telomerase expression in the ALT cells suppressed TSA-mediated ALT phenotype enhancement. Our results show that certain ALT phenotypes become more pronounced when chromatin is decondensed, and also suggest that the ALT mechanism may compete with telomerase for telomere maintenance in cells that lack heterochromatin.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4686653','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4686653"><span>Stable kinetochore–microtubule attachment is sufficient to silence the spindle assembly checkpoint in human cells</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Tauchman, Eric C.; Boehm, Frederick J.; DeLuca, Jennifer G.</p>
<p>2015-01-01</p>
<p>During mitosis, duplicated sister chromatids attach to microtubules emanating from opposing sides of the bipolar spindle through large protein complexes called kinetochores. In the absence of stable kinetochore–microtubule attachments, a cell surveillance mechanism known as the spindle assembly checkpoint (SAC) produces an inhibitory signal that prevents anaphase onset. Precisely how the inhibitory SAC signal is extinguished in response to microtubule attachment remains unresolved. To address this, we induced formation of hyper-stable kinetochore–microtubule attachments in human cells using a non-phosphorylatable version of the protein Hec1, a core component of the attachment machinery. We find that stable attachments are sufficient to silence the SAC in the absence of sister kinetochore bi-orientation and strikingly in the absence of detectable microtubule pulling forces or tension. Furthermore, we find that SAC satisfaction occurs despite the absence of large changes in intra-kinetochore distance, suggesting that substantial kinetochore stretching is not required for quenching the SAC signal. PMID:26620470</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24026537','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24026537"><span>MHF1-2/CENP-S-X performs distinct roles in centromere metabolism and genetic recombination.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Bhattacharjee, Sonali; Osman, Fekret; Feeney, Laura; Lorenz, Alexander; Bryer, Claire; Whitby, Matthew C</p>
<p>2013-09-11</p>
<p>The histone-fold proteins Mhf1/CENP-S and Mhf2/CENP-X perform two important functions in vertebrate cells. First, they are components of the constitutive centromere-associated network, aiding kinetochore assembly and function. Second, they work with the FANCM DNA translocase to promote DNA repair. However, it has been unclear whether there is crosstalk between these roles. We show that Mhf1 and Mhf2 in fission yeast, as in vertebrates, serve a dual function, aiding DNA repair/recombination and localizing to centromeres to promote chromosome segregation. Importantly, these functions are distinct, with the former being dependent on their interaction with the FANCM orthologue Fml1 and the latter not. Together with Fml1, they play a second role in aiding chromosome segregation by processing sister chromatid junctions. However, a failure of this activity does not manifest dramatically increased levels of chromosome missegregation due to the Mus81-Eme1 endonuclease, which acts as a failsafe to resolve DNA junctions before the end of mitosis.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20116100','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20116100"><span>Testing the genotoxicity of coking wastewater using Vicia faba and Hordeum vulgare bioassays.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Dong, Yiru; Zhang, Jintun</p>
<p>2010-07-01</p>
<p>The coking wastewater induces severe environmental problems in China, however, its toxicity has not been well known. In the present study, the genotoxicity of coking wastewater was studied using Vicia faba and Hordeum vulgare root tip cytogenetic bioassays. Results show that the tested coking wastewater decreased the mitotic index, and significantly enhanced the frequencies of micronucleus, sister chromatid exchange and pycnotic cell in concentration-dependent manners. Exposure to the same concentration wastewater, the increasing ratios of above genetic injuries were higher in V. faba than that in H. vulgare. The results imply that coking wastewater is a genotoxic agent in plant cells and exposure to the wastewater in environment may pose a potential genotoxic risk to organisms. It also suggests that both bioassays can be used for testing the genotoxicity of coking wastewater, but the V. faba assay is more sensitive than H. vulgare assay during the process. Copyright (c) 2010. Published by Elsevier Inc.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2779255','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2779255"><span>Ase1/Prc1-dependent spindle elongation corrects merotely during anaphase in fission yeast</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Courtheoux, Thibault; Gay, Guillaume; Tournier, Sylvie</p>
<p>2009-01-01</p>
<p>Faithful segregation of sister chromatids requires the attachment of each kinetochore (Kt) to microtubules (MTs) that extend from opposite spindle poles. Merotelic Kt orientation is a Kt–MT misattachment in which a single Kt binds MTs from both spindle poles rather than just one. Genetic induction of merotelic Kt attachment during anaphase in fission yeast resulted in intra-Kt stretching followed by either correction or Kt disruption. Laser ablation of spindle MTs revealed that intra-Kt stretching and merotelic correction were dependent on MT forces. The presence of multiple merotelic chromosomes linearly antagonized the spindle elongation rate, and this phenomenon could be solved numerically using a simple force balance model. Based on the predictions of our mechanical model, we provide in vivo evidence that correction of merotelic attachment in anaphase is tension dependent and requires an Ase1/Prc1-dependent mechanism that prevents spindle collapse and thus asymmetric division and/or the appearance of the cut phenotype. PMID:19948483</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23285752','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23285752"><span>[Effects of oil-refining microbes (genus Acinetobacter) on cytogenetical structures of human lymphocytes in cell cultures].</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Il'inskikh, N N; Il'inskikh, E N; Il'inskikh, I N</p>
<p>2012-01-01</p>
<p>The objective of this study was to assess ability of oil-refining bacteria Acinetobacter calcoaceticus and A. valentis to induce karyopathological abnormalities and chromosomal aberrations in human lymphocyte cultures. It was found that the cultures infected with A. calcoaceticus showed significantly high frequencies of cytogenetical effects and chromosomal aberrant cells as compared to the intact cultures and cultures infected with A. valentis. The most of chromosomal aberrations, mainly chromatid aberrations, were located in 1 and 2 chromosomes. Moreover, the aberrations were detected in some specific chromosome areas. Abnormalities of mitotic cell division and nucleus morphology were determined in lymphocyte cultures infected with A. calcoaceticus. There were found significantly high frequencies of cells with micronuclei, nucleus protrusions, anaphase or metaphase chromosome and chromosomal fragments lagging as well as multipolar and C-mitoses. Thus, the oil-refining bacteria A. calcoaceticus in contrast to A. valentis demonstrated strong genotoxic effects in human lymphocyte cultures in vitro.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21787658','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21787658"><span>In vitro effect of the antimalarial drug proguanil hydrochloride on viability and DNA damage in human peripheral blood lymphocytes.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Gajski, Goran; Dinter, Domagoj; Garaj-Vrhovac, Vera</p>
<p>2010-11-01</p>
<p>This study aimed to evaluate the effect of proguanil, a chemical substance used for treatment and prevention of malaria on viability and DNA integrity in human lymphocytes in vitro. Two different concentrations of proguanil obtained from the plasma concentrations were used: 130ng/ml used for prophylactic treatment and 520ng/ml used in treatment of malaria. Testing was done with and without metabolic activation. Viability of lymphocytes decreased in time and dose dependent manner. Comet assay parameters showed similar effects, indicating that some damage to DNA molecule can occur. Frequency of sister chromatid exchanges did not show significant deviation from the control samples. As for the proliferation kinetics no significant changes were noticed. Since majority of DNA damaging effect is induced after metabolic activation it is to be concluded that activity of proguanil is dependent upon the active metabolite cycloguanil and that monitoring should be conducted especially among frequent travellers. Copyright © 2010 Elsevier B.V. All rights reserved.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/7885371','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/7885371"><span>The improved Allium/Vicia root tip micronucleus assay for clastogenicity of environmental pollutants.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Ma, T H; Xu, Z; Xu, C; McConnell, H; Rabago, E V; Arreola, G A; Zhang, H</p>
<p>1995-04-01</p>
<p>The meristematic mitotic cells of plant roots are appropriate and efficient cytogenetic materials for the detection of clastogenicity of environmental pollutants, especially for in situ monitoring of water contaminants. Among several cytological endpoints in these fast dividing cells, such as chromosome/chromatid aberrations, sister-chromatid exchanges and micronuclei, the most effective and simplest indicator of cytological damage is micronucleus formation. Although the Allium cepa and Vicia faba root meristem micronucleus assays (Allium/Vicia root MCN) have been used in clastogenicity studies about 12 times by various authors in the last 25 years, there is no report on the comparison of the efficiency of these two plant systems and in different cell populations (meristem and F1) of the root tip as well as under adequate recovery duration. In order to maximize the efficiency of these bioassays, the current study was designed to compare the Allium and the Vicia root MCN assays on the basis of chromosome length, peak sensitivity of the mitotic cells, and the regions of the root tip where the MCN are formed. The total length of the 2n complement of Allium chromosomes is 14.4 microns and the total length of the 2n complement of Vicia is 9.32 microns. The peak sensitivity determined by serial fixation at 12-h intervals after 100 R of X-irradiation is 44 h. The slope of the X-ray dose-response curve of Allium roots derived from the meristematic regions was lower than that derived from cells in the F1 region. Higher efficiency was also demonstrated when the MCN frequencies were scored from the F1 cells in both Allium and Vicia treated with formaldehyde (FA), mitomycin C (MMC), and maleic hydrazide (MH). The results indicated that scoring of MCN frequencies from the F1 cell region of the root tip was more efficient than scoring from the meristematic region. The X-ray linear regression dose-response curves were established in both Allium and Vicia cell systems and the coefficients of correlations, slope values were used to verify the reliability and efficiency of these two plant cell systems. Based on the dose-response slope value of 0.894 for Allium and 0.643 for Vicia, the Allium root MCN was a more efficient test system. The greater sensitivity of the Allium roots is probably due to the greater total length of the diploid complement and the higher number of metacentric chromosomes.(ABSTRACT TRUNCATED AT 400 WORDS)</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/12209188','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/12209188"><span>NTP technical report on the toxicity studies of Pesticide/Fertilizer Mixtures Administered in Drinking Water to F344/N Rats and B6C3F1 Mice.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Yang, R.</p>
<p>1993-08-01</p>
<p>Toxicity studies were performed with pesticide and fertilizer mixtures representative of groundwater contamination found in California and Iowa. The California mixture was composed of aldicarb, atrazine, 1,2-dibromo-3-chloropropane, 1,2- dichloropropane, ethylene dibromide, simazine, and ammonium nitrate. The Iowa mixture contained alachlor, atrazine, cyanazine, metolachlor, metribuzin, and ammonium nitrate. The mixtures were administered in drinking water (with 512 ppm propylene glycol) to F344/N rats and B6C3F1 mice of each sex at concentrations ranging from 0.1x to 100x, where 1x represented the median concentrations of the individual chemicals found in studies of groundwater contamination from normal agricultural activities. This report focuses primarily on 26-week toxicity studies describing histopathology, clinical pathology, neurobehavior/neuropathology, and reproductive system effects. The genetic toxicity of the mixtures was assessed by determining the frequency of micronuclei in peripheral blood of mice and evaluating micronuclei and sister chromatid exchanges in splenocytes from female mice and male rats. Additional studies with these mixtures that are briefly reviewed in this report include teratology studies with Sprague-Dawley rats and continuous breeding studies with CD-1 Swiss mice. In 26-week drinking water studies of the California and the Iowa mixtures, all rats (10 per sex and group) survived to the end of the studies, and there were no significant effects on body weight gains. Water consumption was not affected by the pesticide/fertilizer contaminants, and there were no clinical signs of toxicity or neurobehavioral effects as measured by a functional observational battery, motor activity evaluations, thermal sensitivity evaluations, and startle response. There were no clear adverse effects noted in clinical pathology (including serum cholinesterase activity), organ weight, reproductive system, or histopathologic evaluations, although absolute and relative liver weights were marginally increased with increasing exposure concentration in both male and female rats consuming the Iowa mixture. In 26-week drinking water studies in mice, one male receiving the California mixture at 100x died during the study, and one control female and one female in the 100x group in the Iowa mixture study also died early. It could not be determined if the death of either of the mice in the 100x groups was related to consumption of the pesticide/fertilizer mixtures. Water consumption and body weight gains were not affected in these studies, and no signs of toxicity were noted in clinical observations or in neurobehavioral assessments. No clear adverse effects were noted in clinical pathology, reproductive system, organ weight, or histopathologic evaluations of exposed mice. The pesticide/fertilizer mixtures, when tested over a concentration range similar to that used in the 26-week studies, were found to have no effects in teratology studies or in a continuous breeding assay examining reproductive and developmental toxicity. The California and Iowa pesticide mixtures were tested for induction of micronuclei in peripheral blood erythrocytes of female mice. Results of tests with the California mixture were negative. Significant increases in micronucleated normochromatic erythrocytes were seen at the two-highest concentrations (10x and 100x) of the Iowa mixture, but the increases were within the normal range of micronuclei in historical control animals. Splenocytes of male rats and female mice exposed to these mixtures were examined for micronucleus and sister chromatid exchange frequencies. Sister chromatid exchange frequencies were marginally increased in rats and mice receiving the California mixture, but neither species exhibited increased frequencies of micronucleated splenocytes. None of these changes were considered to have biological importance. In summary, studies of potential toxicity associated with the consumption of mixtures of pesticides and a fertilizer representative of groundwater contamination in agriculturative of groundwater contamination in agricultural areas of Iowa and California failed to demonstrate any significant adverse effects in rats or mice receiving the mixtures in drinking water at concentrations as high as 100 times the median concentrations of the individual chemicals determined by groundwater surveys. NOTE: These studies were supported in part by funds from the Comprehensive Environmental Response, Compensation, and Liability Act trust fund (Superfund) by an interagency agreement with the Agency for Toxic Substances and Disease Registry, U.S. Public Health Service.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4286542','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4286542"><span>Polyoma small T antigen triggers cell death via mitotic catastrophe</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Fernando, Arun T Pores; Andrabi, Shaida; Cizmecioglu, Onur; Zhu, Cailei; Livingston, David M.; Higgins, Jonathan M.G; Schaffhausen, Brian S; Roberts, Thomas M</p>
<p>2014-01-01</p>
<p>Polyoma small T antigen (PyST), an early gene product of the polyoma virus, has been shown to cause cell death in a number of mammalian cells in a protein phosphatase 2A (PP2A)-dependent manner. In the current study, using a cell line featuring regulated expression of PyST, we found that PyST arrests cells in mitosis. Live-cell and immunofluorescence studies showed that the majority of the PyST-expressing cells were arrested in prometaphase with almost no cells progressing beyond metaphase. These cells exhibited defects in chromosomal congression, sister chromatid cohesion and spindle positioning, resulting in the activation of the Spindle Assembly Checkpoint (SAC). Prolonged mitotic arrest then led to cell death via mitotic catastrophe. Cell cycle inhibitors that block cells in G1/S prevented PyST-induced death. PyST-induced cell death that occurs during M is not dependent on p53 status. These data suggested, and our results confirmed that, PP2A inhibition could be used to preferentially kill cancer cells with p53 mutations that proliferate normally in the presence of cell cycle inhibitors. PMID:24998850</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5354518','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5354518"><span>The Ndc80 complex bridges two Dam1 complex rings</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Kim, Jae ook; Zelter, Alex; Umbreit, Neil T; Bollozos, Athena; Riffle, Michael; Johnson, Richard; MacCoss, Michael J; Asbury, Charles L; Davis, Trisha N</p>
<p>2017-01-01</p>
<p>Strong kinetochore-microtubule attachments are essential for faithful segregation of sister chromatids during mitosis. The Dam1 and Ndc80 complexes are the main microtubule binding components of the Saccharomyces cerevisiae kinetochore. Cooperation between these two complexes enhances kinetochore-microtubule coupling and is regulated by Aurora B kinase. We show that the Ndc80 complex can simultaneously bind and bridge across two Dam1 complex rings through a tripartite interaction, each component of which is regulated by Aurora B kinase. Mutations in any one of the Ndc80p interaction regions abrogates the Ndc80 complex’s ability to bind two Dam1 rings in vitro, and results in kinetochore biorientation and microtubule attachment defects in vivo. We also show that an extra-long Ndc80 complex, engineered to space the two Dam1 rings further apart, does not support growth. Taken together, our work suggests that each kinetochore in vivo contains two Dam1 rings and that proper spacing between the rings is vital. DOI: http://dx.doi.org/10.7554/eLife.21069.001 PMID:28191870</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3343459','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3343459"><span>Cohesin-SA1 deficiency drives aneuploidy and tumourigenesis in mice due to impaired replication of telomeres</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Remeseiro, Silvia; Cuadrado, Ana; Carretero, María; Martínez, Paula; Drosopoulos, William C; Cañamero, Marta; Schildkraut, Carl L; Blasco, María A; Losada, Ana</p>
<p>2012-01-01</p>
<p>Cohesin is a protein complex originally identified for its role in sister chromatid cohesion, although increasing evidence portrays it also as a major organizer of interphase chromatin. Vertebrate cohesin consists of Smc1, Smc3, Rad21/Scc1 and either stromal antigen 1 (SA1) or SA2. To explore the functional specificity of these two versions of cohesin and their relevance for embryonic development and cancer, we generated a mouse model deficient for SA1. Complete ablation of SA1 results in embryonic lethality, while heterozygous animals have shorter lifespan and earlier onset of tumourigenesis. SA1-null mouse embryonic fibroblasts show decreased proliferation and increased aneuploidy as a result of chromosome segregation defects. These defects are not caused by impaired centromeric cohesion, which depends on cohesin-SA2. Instead, they arise from defective telomere replication, which requires cohesion mediated specifically by cohesin-SA1. We propose a novel mechanism for aneuploidy generation that involves impaired telomere replication upon loss of cohesin-SA1, with clear implications in tumourigenesis. PMID:22415365</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20306073','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20306073"><span>Genotoxicity surveillance programme in workers dismantling World War I chemical ammunition.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Mateuca, R A; Carton, C; Roelants, M; Roesems, S; Lison, D; Kirsch-Volders, M</p>
<p>2010-06-01</p>
<p>To evaluate the effectiveness of personal protective measures in a dismantling plant for chemical weapons from World War I of the Belgian Defence. Seventeen NIOSH level B-equipped plant workers exposed to arsenic trichloride (AsCl(3)) in combination with phosgene or hydrogen cyanide (HCN) were compared to 24 NIOSH level C-protected field workers occasionally exposed to genotoxic chemicals (including AsCl(3)-phosgene/HCN) when collecting chemical ammunition, and 19 matched referents. Chromosomal aberrations (CA), micronuclei (MNCB and MNMC), sister chromatid exchanges (SCE) and high frequency cells (HFC) were analysed in peripheral blood lymphocytes. Urinary arsenic levels and genetic polymorphisms in major DNA repair enzymes (hOGG1(326), XRCC1(399), XRCC3(241)) were also assessed. SCE and HFC levels were significantly higher in plant-exposed versus referent subjects, but MNCB and MNMC were not different. MNCB, SCE and HFC levels were significantly higher and MNMC levels significantly lower in field-exposed workers versus referents. AsCl(3) exposure was not correlated with genotoxicity biomarkers. Protective measures for plant-exposed workers appear adequate, but protection for field-exposed individuals could be improved.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3123689','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3123689"><span>Blood-Based Detection of Radiation Exposure in Humans Based on Novel Phospho-Smc1 ELISA</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Ivey, Richard G.; Moore, Heather D.; Voytovich, Uliana J.; Thienes, Cortlandt P.; Lorentzen, Travis D.; Pogosova-Agadjanyan, Era L.; Frayo, Shani; Izaguirre, Venissa K.; Lundberg, Sally J.; Hedin, Lacey; Badiozamani, Kas Ray; Hoofnagle, Andrew N.; Stirewalt, Derek L.; Wang, Pei; Georges, George E.; Gopal, Ajay K.; Paulovich, Amanda G.</p>
<p>2011-01-01</p>
<p>The structural maintenance of chromosome 1 (Smc1) protein is a member of the highly conserved cohesin complex and is involved in sister chromatid cohesion. In response to ionizing radiation, Smc1 is phosphorylated at two sites, Ser-957 and Ser-966, and these phosphorylation events are dependent on the ATM protein kinase. In this study, we describe the generation of two novel ELISAs for quantifying phospho-Smc1Ser-957 and phospho-Smc1Ser-966. Using these novel assays, we quantify the kinetic and biodosimetric responses of human cells of hematological origin, including immortalized cells, as well as both quiescent and cycling primary human PBMC. Additionally, we demonstrate a robust in vivo response for phospho-Smc1Ser-957 and phospho-Smc1Ser-966 in lymphocytes of human patients after therapeutic exposure to ionizing radiation, including total-body irradiation, partial-body irradiation, and internal exposure to 131I. These assays are useful for quantifying the DNA damage response in experimental systems and potentially for the identification of individuals exposed to radiation after a radiological incident. PMID:21388270</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/15937225','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/15937225"><span>Visualization of diffuse centromeres with centromere-specific histone H3 in the holocentric plant Luzula nivea.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Nagaki, Kiyotaka; Kashihara, Kazunari; Murata, Minoru</p>
<p>2005-07-01</p>
<p>Although holocentric species are scattered throughout the plant and animal kingdoms, only holocentric chromosomes of the nematode worm Caenorhabditis elegans have been analyzed with centromeric protein markers. In an effort to determine the holocentric structure in plants, we investigated the snowy woodrush Luzula nivea. From the young roots, a cDNA encoding a putative centromere-specific histone H3 (LnCENH3) was successfully isolated based on sequence similarity among plant CENH3s. The deduced amino acid sequence was then used to raise an anti-LnCENH3 antibody. Immunostaining clearly revealed the diffuse centromere-like structure that appears in the linear shape at prophase to telophase. Furthermore, it was shown that the amount of LnCENH3 decreased significantly at interphase. The polar side positioning on each chromatid at metaphase to anaphase also confirmed that LnCENH3 represents one of the centromere-specific proteins in L. nivea. These data from L. nivea are compared with those from C. elegans, and common features of holocentric chromosomes are discussed.</p>
</li>
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<ol class="result-class" start="381">
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17371833','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17371833"><span>The Aurora kinase Ipl1 maintains the centromeric localization of PP2A to protect cohesin during meiosis.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Yu, Hong-Guo; Koshland, Douglas</p>
<p>2007-03-26</p>
<p>Homologue segregation during the first meiotic division requires the proper spatial regulation of sister chromatid cohesion and its dissolution along chromosome arms, but its protection at centromeric regions. This protection requires the conserved MEI-S332/Sgo1 proteins that localize to centromeric regions and also recruit the PP2A phosphatase by binding its regulatory subunit, Rts1. Centromeric Rts1/PP2A then locally prevents cohesion dissolution possibly by dephosphorylating the protein complex cohesin. We show that Aurora B kinase in Saccharomyces cerevisiae (Ipl1) is also essential for the protection of meiotic centromeric cohesion. Coupled with a previous study in Drosophila melanogaster, this meiotic function of Aurora B kinase appears to be conserved among eukaryotes. Furthermore, we show that Sgo1 recruits Ipl1 to centromeric regions. In the absence of Ipl1, Rts1 can initially bind to centromeric regions but disappears from these regions after anaphase I onset. We suggest that centromeric Ipl1 ensures the continued centromeric presence of active Rts1/PP2A, which in turn locally protects cohesin and cohesion.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17165625','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17165625"><span>Immunocytogenetic effects of gonadotropin releasing hormone analogue: Triptorelin Pamoate (Decapeptyl) during in vitro fertilization treatment.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Al-Qashi, S; Al-Qaoud, K M; Ja'fer, M; Khali, A M</p>
<p>2006-10-01</p>
<p>In this study, the immunocytogenetic effects of Decapeptyl (Triptorelin Pamoate) were assessed in the peripheral blood lymphocytes of females undergoing in vitro fertilization (IVF) treatment. Blood samples were taken from 34 females (23 treated and 11 controls), cultured and examined for sister chromatid exchanges (SCE) and cell replication index (CRI). The SCE frequency increased around ovulation time in the controls, and around the time of human chorionic gonadotropin administration in the IVF group. However, the SCE rate was significantly higher in the latter group. Furthermore, the white blood cells (WBC) count was significantly higher on the day of ovum pick up compared to the day preceding luteinizing hormone (LH) and follicle stimulating hormone (FSH) treatment. Similar observations were recorded with respect to phagocytic activity tested by nitroblue tetrazolium (NBT) assay. The nitric oxide production abilities of macrophages were not significantly changed in the LH, FSH-treated group relative to its control. Finally, the 50% complement hemolytic activity (CH50) assay results indicated that Decapeptyl lacks a significant potential to affect the complement system.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26923598','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26923598"><span>Crystal Structure of the Cohesin Gatekeeper Pds5 and in Complex with Kleisin Scc1.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Lee, Byung-Gil; Roig, Maurici B; Jansma, Marijke; Petela, Naomi; Metson, Jean; Nasmyth, Kim; Löwe, Jan</p>
<p>2016-03-08</p>
<p>Sister chromatid cohesion is mediated by cohesin, whose Smc1, Smc3, and kleisin (Scc1) subunits form a ring structure that entraps sister DNAs. The ring is opened either by separase, which cleaves Scc1 during anaphase, or by a releasing activity involving Wapl, Scc3, and Pds5, which bind to Scc1 and open its interface with Smc3. We present crystal structures of Pds5 from the yeast L. thermotolerans in the presence and absence of the conserved Scc1 region that interacts with Pds5. Scc1 binds along the spine of the Pds5 HEAT repeat fold and is wedged between the spine and C-terminal hook of Pds5. We have isolated mutants that confirm the observed binding mode of Scc1 and verified their effect on cohesin by immunoprecipitation and calibrated ChIP-seq. The Pds5 structure also reveals architectural similarities to Scc3, the other large HEAT repeat protein of cohesin and, most likely, Scc2. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2683758','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2683758"><span>Chromosome congression by kinesin-5 motor-mediated disassembly of longer kinetochore microtubules</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Gardner, Melissa K; Bouck, David C.; Paliulis, Leocadia V.; Meehl, Janet B.; O’Toole, Eileen T.; Haase, Julian; Soubry, Adelheid; Joglekar, Ajit P.; Winey, Mark; Salmon, Edward D.; Bloom, Kerry; Odde, David J.</p>
<p>2008-01-01</p>
<p>Summary During mitosis, sister chromatids congress to the spindle equator and are subsequently segregated via attachment to dynamic kinetochore microtubule (kMT) plus-ends. A major question is how kMT plus-end assembly is spatially regulated to achieve chromosome congression. Here we find in budding yeast that the widely-conserved kinesin-5 sliding motor proteins, Cin8p and Kip1p, mediate chromosome congression by suppressing kMT plus-end assembly of longer kMTs. Of the two, Cin8p is the major effector and its activity requires a functional motor domain. In contrast, the depolymerizing kinesin-8 motor Kip3p plays a minor role in spatial regulation of yeast kMT assembly. Our analysis identified a model where kinesin-5 motors bind to kMTs, move to kMT plus ends, and upon arrival at a growing plus-end promote net kMT plus-end disassembly. In conclusion, we find that length-dependent control of net kMT assembly by kinesin-5 motors yields a simple and stable self-organizing mechanism for chromosome congression. PMID:19041752</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3172173','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3172173"><span>RAD21L, a novel cohesin subunit implicated in linking homologous chromosomes in mammalian meiosis</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Lee, Jibak</p>
<p>2011-01-01</p>
<p>Cohesins are multi-subunit protein complexes that regulate sister chromatid cohesion during mitosis and meiosis. Here we identified a novel kleisin subunit of cohesins, RAD21L, which is conserved among vertebrates. In mice, RAD21L is expressed exclusively in early meiosis: it apparently replaces RAD21 in premeiotic S phase, becomes detectable on the axial elements in leptotene, and stays on the axial/lateral elements until mid pachytene. RAD21L then disappears, and is replaced with RAD21. This behavior of RAD21L is unique and distinct from that of REC8, another meiosis-specific kleisin subunit. Remarkably, the disappearance of RAD21L at mid pachytene correlates with the completion of DNA double-strand break repair and the formation of crossovers as judged by colabeling with molecular markers, γ-H2AX, MSH4, and MLH1. RAD21L associates with SMC3, STAG3, and either SMC1α or SMC1β. Our results suggest that cohesin complexes containing RAD21L may be involved in synapsis initiation and crossover recombination between homologous chromosomes. PMID:21242291</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4752329','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4752329"><span>Chromosome Synapsis Alleviates Mek1-Dependent Suppression of Meiotic DNA Repair</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Subramanian, Vijayalakshmi V.; MacQueen, Amy J.; Vader, Gerben; Shinohara, Miki; Sanchez, Aurore; Borde, Valérie; Shinohara, Akira; Hochwagen, Andreas</p>
<p>2016-01-01</p>
<p>Faithful meiotic chromosome segregation and fertility require meiotic recombination between homologous chromosomes rather than the equally available sister chromatid, a bias that in Saccharomyces cerevisiae depends on the meiotic kinase, Mek1. Mek1 is thought to mediate repair template bias by specifically suppressing sister-directed repair. Instead, we found that when Mek1 persists on closely paired (synapsed) homologues, DNA repair is severely delayed, suggesting that Mek1 suppresses any proximal repair template. Accordingly, Mek1 is excluded from synapsed homologues in wild-type cells. Exclusion requires the AAA+-ATPase Pch2 and is directly coupled to synaptonemal complex assembly. Stage-specific depletion experiments further demonstrate that DNA repair in the context of synapsed homologues requires Rad54, a repair factor inhibited by Mek1. These data indicate that the sister template is distinguished from the homologue primarily by its closer proximity to inhibitory Mek1 activity. We propose that once pairing or synapsis juxtaposes homologues, exclusion of Mek1 is necessary to avoid suppression of all templates and accelerate repair progression. PMID:26870961</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21242291','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21242291"><span>RAD21L, a novel cohesin subunit implicated in linking homologous chromosomes in mammalian meiosis.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Lee, Jibak; Hirano, Tatsuya</p>
<p>2011-01-24</p>
<p>Cohesins are multi-subunit protein complexes that regulate sister chromatid cohesion during mitosis and meiosis. Here we identified a novel kleisin subunit of cohesins, RAD21L, which is conserved among vertebrates. In mice, RAD21L is expressed exclusively in early meiosis: it apparently replaces RAD21 in premeiotic S phase, becomes detectable on the axial elements in leptotene, and stays on the axial/lateral elements until mid pachytene. RAD21L then disappears, and is replaced with RAD21. This behavior of RAD21L is unique and distinct from that of REC8, another meiosis-specific kleisin subunit. Remarkably, the disappearance of RAD21L at mid pachytene correlates with the completion of DNA double-strand break repair and the formation of crossovers as judged by colabeling with molecular markers, γ-H2AX, MSH4, and MLH1. RAD21L associates with SMC3, STAG3, and either SMC1α or SMC1β. Our results suggest that cohesin complexes containing RAD21L may be involved in synapsis initiation and crossover recombination between homologous chromosomes.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27008552','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27008552"><span>Condensin I and II behaviour in interphase nuclei and cells undergoing premature chromosome condensation.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Zhang, Tao; Paulson, James R; Bakhrebah, Muhammed; Kim, Ji Hun; Nowell, Cameron; Kalitsis, Paul; Hudson, Damien F</p>
<p>2016-05-01</p>
<p>Condensin is an integral component of the mitotic chromosome condensation machinery, which ensures orderly segregation of chromosomes during cell division. In metazoans, condensin exists as two complexes, condensin I and II. It is not yet clear what roles these complexes may play outside mitosis, and so we have examined their behaviour both in normal interphase and in premature chromosome condensation (PCC). We find that a small fraction of condensin I is retained in interphase nuclei, and our data suggests that this interphase nuclear condensin I is active in both gene regulation and chromosome condensation. Furthermore, live cell imaging demonstrates condensin II dramatically increases on G1 nuclei following completion of mitosis. Our PCC studies show condensins I and II and topoisomerase II localise to the chromosome axis in G1-PCC and G2/M-PCC, while KIF4 binding is altered. Individually, condensins I and II are dispensable for PCC. However, when both are knocked out, G1-PCC chromatids are less well structured. Our results define new roles for the condensins during interphase and provide new information about the mechanism of PCC.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3590994','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3590994"><span>Prophase pathway-dependent removal of cohesin from human chromosomes requires opening of the Smc3–Scc1 gate</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Buheitel, Johannes; Stemmann, Olaf</p>
<p>2013-01-01</p>
<p>Faithful transmission of chromosomes during eukaryotic cell division requires sister chromatids to be paired from their generation in S phase until their separation in M phase. Cohesion is mediated by the cohesin complex, whose Smc1, Smc3 and Scc1 subunits form a tripartite ring that entraps both DNA double strands. Whereas centromeric cohesin is removed in late metaphase by Scc1 cleavage, metazoan cohesin at chromosome arms is displaced already in prophase by proteolysis-independent signalling. Which of the three gates is triggered by the prophase pathway to open has remained enigmatic. Here, we show that displacement of human cohesin from early mitotic chromosomes requires dissociation of Smc3 from Scc1 but no opening of the other two gates. In contrast, loading of human cohesin onto chromatin in telophase occurs through the Smc1–Smc3 hinge. We propose that the use of differently regulated gates for loading and release facilitates unidirectionality of DNA's entry into and exit from the cohesin ring. PMID:23361318</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/15887256','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/15887256"><span>Controversial cytogenetic observations in mammalian somatic cells exposed to extremely low frequency electromagnetic radiation: a review and future research recommendations.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Vijayalaxmi; Obe, Guenter</p>
<p>2005-07-01</p>
<p>During the years 1990-2003, a large number of investigations were conducted using animals, cultured rodent and human cells as well as freshly collected human blood lymphocytes to determine the genotoxic potential of exposure to nonionizing radiation emitted from extremely low frequency electromagnetic fields (EMF). Among the 63 peer reviewed scientific reports, the conclusions from 29 studies (46%) did not indicate increased damage to the genetic material, as assessed from DNA strand breaks, incidence of chromosomal aberrations (CA), micronuclei (MN), and sister chromatid exchanges (SCE), in EMF exposed cells as compared with sham exposed and/or unexposed cells, while those from 14 investigations (22%) have suggested an increase in such damage in EMF exposed cells. The observations from 20 other studies (32%) were inconclusive. This study reviews the investigations published in peer reviewed scientific journals during 1990-2003 and attempts to identify probable reason(s) for the conflicting results. Recommendations are made for future research to address some of the controversial observations. Copyright 2005 Wiley-Liss, Inc.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24656232','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24656232"><span>Molecular mechanisms of homologous chromosome pairing and segregation in plants.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Zhang, Jing; Zhang, Bing; Su, Handong; Birchler, James A; Han, Fangpu</p>
<p>2014-03-20</p>
<p>In most eukaryotic species, three basic steps of pairing, recombination and synapsis occur during prophase of meiosis I. Homologous chromosomal pairing and recombination are essential for accurate segregation of chromosomes. In contrast to the well-studied processes such as recombination and synapsis, many aspects of chromosome pairing are still obscure. Recent progress in several species indicates that the telomere bouquet formation can facilitate homologous chromosome pairing by bringing chromosome ends into close proximity, but the sole presence of telomere clustering is not sufficient for recognizing homologous pairs. On the other hand, accurate segregation of the genetic material from parent to offspring during meiosis is dependent on the segregation of homologs in the reductional meiotic division (MI) with sister kinetochores exhibiting mono-orientation from the same pole, and the segregation of sister chromatids during the equational meiotic division (MII) with kinetochores showing bi-orientation from the two poles. The underlying mechanism of orientation and segregation is still unclear. Here we focus on recent studies in plants and other species that provide insight into how chromosomes find their partners and mechanisms mediating chromosomal segregation. Copyright © 2013. Published by Elsevier Ltd.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=14780','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=14780"><span>Kinetic Analysis of a Molecular Model of the Budding Yeast Cell Cycle</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Chen, Katherine C.; Csikasz-Nagy, Attila; Gyorffy, Bela; Val, John; Novak, Bela; Tyson, John J.</p>
<p>2000-01-01</p>
<p>The molecular machinery of cell cycle control is known in more detail for budding yeast, Saccharomyces cerevisiae, than for any other eukaryotic organism. In recent years, many elegant experiments on budding yeast have dissected the roles of cyclin molecules (Cln1–3 and Clb1–6) in coordinating the events of DNA synthesis, bud emergence, spindle formation, nuclear division, and cell separation. These experimental clues suggest a mechanism for the principal molecular interactions controlling cyclin synthesis and degradation. Using standard techniques of biochemical kinetics, we convert the mechanism into a set of differential equations, which describe the time courses of three major classes of cyclin-dependent kinase activities. Model in hand, we examine the molecular events controlling “Start” (the commitment step to a new round of chromosome replication, bud formation, and mitosis) and “Finish” (the transition from metaphase to anaphase, when sister chromatids are pulled apart and the bud separates from the mother cell) in wild-type cells and 50 mutants. The model accounts for many details of the physiology, biochemistry, and genetics of cell cycle control in budding yeast. PMID:10637314</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/3033033','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/3033033"><span>Lethal genes surviving by mosaicism: a possible explanation for sporadic birth defects involving the skin.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Happle, R</p>
<p>1987-04-01</p>
<p>A genetic concept is advanced to explain the origin of several sporadic syndromes characterized by a mosaic distribution of skin defects. It is postulated that these disorders are due to the action of a lethal gene surviving by mosaicism. The presence of the mutation in the zygote will lead to death of the embryo at an early stage of development. Cells bearing the mutation can survive only in a mosaic state, in close proximity with normal cells. The mosaic may arise either from a gametic half chromatid mutation or from an early somatic mutation. This concept of origin is proposed to apply to the Schimmelpenning-Feuerstein-Mims syndrome, the McCune-Albright syndrome, the Klippel-Trenaunay syndrome, the Sturge-Weber syndrome, and neurocutaneous melanosis. Moreover, this etiologic hypothesis may apply to two other birth defects that have recently been delineated, the Proteus syndrome (partial gigantism of hands or feet, hemihypertrophy, macrocephaly, linear papillomatous epidermal nevus, subcutaneous hemangiomas and lipomas, accelerated growth, and visceral anomalies), and the Delleman-Oorthuys syndrome (orbital cyst, porencephaly, periorbital appendages, and focal aplasia of the skin.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21381055','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21381055"><span>Reduction in fluoride-induced genotoxicity in mouse bone marrow cells after substituting high fluoride-containing water with safe drinking water.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Podder, Santosh; Chattopadhyay, Ansuman; Bhattacharya, Shelley</p>
<p>2011-10-01</p>
<p>Treatment of mice with 15 mg l(-1) sodium fluoride (NaF) for 30 days increased the number of cell death, chromosomal aberrations (CAs) and 'cells with chromatid breaks' (aberrant cells) compared with control. The present study was intended to determine whether the fluoride (F)-induced genotoxicity could be reduced by substituting high F-containing water after 30 days with safe drinking water, containing 0.1 mg F ions l(-1). A significant fall in percentage of CAs and aberrant cells after withdrawal of F-treatment following 30 days of safe water treatment in mice was observed which was highest after 90 days, although their levels still remained significantly high compared with the control group. This observation suggests that F-induced genotoxicity could be reduced by substituting high F-containing water with safe drinking water. Further study is warranted with different doses and extended treatment of safe water to determine whether the induced damages could be completely reduced or not. Copyright © 2011 John Wiley & Sons, Ltd.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28167679','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28167679"><span>Independent mechanisms recruit the cohesin loader protein NIPBL to sites of DNA damage.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Bot, Christopher; Pfeiffer, Annika; Giordano, Fosco; Manjeera, Dharani E; Dantuma, Nico P; Ström, Lena</p>
<p>2017-03-15</p>
<p>NIPBL is required to load the cohesin complex on to DNA. While the canonical role of cohesin is to couple replicated sister chromatids together until the onset of mitosis, it also promotes tolerance to DNA damage. Here, we show that NIPBL is recruited to DNA damage throughout the cell cycle via independent mechanisms, influenced by type of damage. First, the heterochromatin protein HP1γ (also known as CBX3) recruits NIPBL to DNA double-strand breaks (DSBs) through the corresponding HP1-binding motif within the N-terminus. By contrast, the C-terminal HEAT repeat domain is unable to recruit NIPBL to DSBs but independently targets NIPBL to laser microirradiation-induced DNA damage. Each mechanism is dependent on the RNF8 and RNF168 ubiquitylation pathway, while the recruitment of the HEAT repeat domain requires further ATM or ATR activity. Thus, NIPBL has evolved a sophisticated response to damaged DNA that is influenced by the form of damage, suggesting a highly dynamic role for NIPBL in maintaining genomic stability. © 2017. Published by The Company of Biologists Ltd.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3041957','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3041957"><span>Interaction between the helicases genetically linked to Fanconi anemia group J and Bloom's syndrome</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Suhasini, Avvaru N; Rawtani, Nina A; Wu, Yuliang; Sommers, Joshua A; Sharma, Sudha; Mosedale, Georgina; North, Phillip S; Cantor, Sharon B; Hickson, Ian D; Brosh, Robert M</p>
<p>2011-01-01</p>
<p>Bloom's syndrome (BS) and Fanconi anemia (FA) are autosomal recessive disorders characterized by cancer and chromosomal instability. BS and FA group J arise from mutations in the BLM and FANCJ genes, respectively, which encode DNA helicases. In this work, FANCJ and BLM were found to interact physically and functionally in human cells and co-localize to nuclear foci in response to replication stress. The cellular level of BLM is strongly dependent upon FANCJ, and BLM is degraded by a proteasome-mediated pathway when FANCJ is depleted. FANCJ-deficient cells display increased sister chromatid exchange and sensitivity to replication stress. Expression of a FANCJ C-terminal fragment that interacts with BLM exerted a dominant negative effect on hydroxyurea resistance by interfering with the FANCJ–BLM interaction. FANCJ and BLM synergistically unwound a DNA duplex substrate with sugar phosphate backbone discontinuity, but not an ‘undamaged' duplex. Collectively, the results suggest that FANCJ catalytic activity and its effect on BLM protein stability contribute to preservation of genomic stability and a normal response to replication stress. PMID:21240188</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/5498590-formaldehyde-induced-acentric-chromosome-fragments-chromosome-stickiness-chortophaga-neuroblasts','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/5498590-formaldehyde-induced-acentric-chromosome-fragments-chromosome-stickiness-chortophaga-neuroblasts"><span>Formaldehyde-induced acentric chromosome fragments and chromosome stickiness in Chortophaga neuroblasts</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Dowd, M.A.; Gaulden, M.E.; Proctor, B.L.</p>
<p>1986-01-01</p>
<p>Embryos of the grasshopper Chortophaga viridifasciata were exposed in vitro to formaldehyde (FA), as formalin, at concentrations ranging from 10/sup -8/ M (0.0003 ppm) to 10/sup -3/ M (30 ppm) at 38/sup 0/C. A low frequency of distinct acentric chromosome fragments was observed in the neuroblasts after 1 hr exposure to 7.5 x 10/sup -4/ or 10/sup -3/ M FA plus 3 hr recovery, but not at lower concentrations, even with 4 hr exposure. Neuroblasts with sticky chromosomes were observed at 10/sup -4/, 7.5 x 10/sup -4/, and 10/sup -3/ M FA, the percent of cells with slight, moderate, ormore » severe stickiness varying with FA concentrations. Fragments were associated with the sticky chromosomes. It is concluded that the distinct acentric fragments induced by FA result from breakage at a single sticky point (slight stickiness) between separating sister chromatids. The chromosome effects observed probably result from the action of daughter products that are formed by the interaction of FA with culture medium components, especially the fetal calf serum.« less</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2171634','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2171634"><span>Histone H1 is essential for mitotic chromosome architecture and segregation in Xenopus laevis egg extracts</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Maresca, Thomas J.; Freedman, Benjamin S.; Heald, Rebecca</p>
<p>2005-01-01</p>
<p>During cell division, condensation and resolution of chromosome arms and the assembly of a functional kinetochore at the centromere of each sister chromatid are essential steps for accurate segregation of the genome by the mitotic spindle, yet the contribution of individual chromatin proteins to these processes is poorly understood. We have investigated the role of embryonic linker histone H1 during mitosis in Xenopus laevis egg extracts. Immunodepletion of histone H1 caused the assembly of aberrant elongated chromosomes that extended off the metaphase plate and outside the perimeter of the spindle. Although functional kinetochores assembled, aligned, and exhibited poleward movement, long and tangled chromosome arms could not be segregated in anaphase. Histone H1 depletion did not significantly affect the recruitment of known structural or functional chromosomal components such as condensins or chromokinesins, suggesting that the loss of H1 affects chromosome architecture directly. Thus, our results indicate that linker histone H1 plays an important role in the structure and function of vertebrate chromosomes in mitosis. PMID:15967810</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/servlets/purl/932500','SCIGOV-STC'); return false;" href="https://www.osti.gov/servlets/purl/932500"><span>Promotion of Homologous Recombination and Genomic Stability byRAD51AP1 via RAD51 Recombinase Enhancement</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Wiese, Claudia; Dray, Eloise; Groesser, Torsten</p>
<p>2007-04-11</p>
<p>Homologous recombination (HR) repairs chromosome damage and is indispensable for tumor suppression in humans. RAD51 mediates the DNA strand pairing step in HR. RAD51AP1 (RAD51 Associated Protein 1) is a RAD51-interacting protein whose function has remained elusive. Knockdown of RAD51AP1 in human cells by RNA interference engenders sensitivity to different types of genotoxic stress. Moreover, RAD51AP1-depleted cells are impaired for the recombinational repair of a DNA double-strand break and exhibit chromatid breaks both spontaneously and upon DNA damaging treatment. Purified RAD51AP1 binds dsDNA and RAD51, and it greatly stimulates the RAD51-mediated D-loop reaction. Biochemical and cytological results show that RAD51AP1more » functions at a step subsequent to the assembly of the RAD51-ssDNA nucleoprotein filament. Our findings provide the first evidence that RAD51AP1 helps maintain genomic integrity via RAD51 recombinase enhancement.« less</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4606630','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4606630"><span>Role of micronucleus in oral exfoliative cytology</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Shashikala, R.; Indira, A. P.; Manjunath, G. S.; rao, K. Arathi; Akshatha, B. K.</p>
<p>2015-01-01</p>
<p>In the last few years, the interest for oral cytology as a diagnostic and prognostic methodology, for monitoring patients in oral potentially malignant disorders and oral cancer has re-emerged substantially. In 1983, buccal mucosal micronuclei assay was first proposed to evaluate genetic instability. There are biomarkers that predict if a potentially malignant disorder is likely to develop into an aggressive tumor. These genotoxic and carcinogenic chemicals have been reported to be potent clastogenic and mutagenic agents which are thought to be responsible for the induction of chromatid/chromosomal aberrations resulting in the production of micronuclei. Various studies have concluded that the gradual increase in micronucleus (MN) counts from normal oral mucosa to potentially malignant disorders to oral carcinoma suggested a link of this biomarker with neoplastic progression. MN scoring can be used as a biomarker to identify different preneoplastic conditions much earlier than the manifestations of clinical features and might specifically be exploited in the screening of high-risk population for a specific cancer. Hence, it can be used as a screening prognostic and educational tool in community centers of oral cancer. PMID:26538888</p>
</li>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27888426','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27888426"><span>Evaluation of herbicides action on plant bioindicators by genetic biomarkers: a review.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>de Souza, Cleiton Pereira; Guedes, Thays de Andrade; Fontanetti, Carmem Silvia</p>
<p>2016-12-01</p>
<p>The use of pesticides has increased worldwide, owing to the demand for products of good quality and to satisfy a growing population. Herbicides represent almost half of the total amount of pesticides used. Although important to the reduction of costs and an increase of productivity, their indiscriminate use, as well as that of the other pesticides, is a global environmental problem, since they affect the living organisms. To evaluate the damage caused by herbicides to the environment, different organisms have been used as bioindicators, especially higher plants, due to several advantages. This is a literature review on herbicidal actions in plant bioindicators, as assessed by genetic biomarkers. Also, the present manuscript aimed to characterize the main organisms (Allium cepa, Vicia faba and Tradescantia spp.) and the most used biomarkers (mitotic index, chromosome aberrations, micronuclei, sister chromatid exchange and mutations). We concluded that herbicides induce cytotoxicity and genotoxicity in the assessed bioindicators. The data corroborate the existing warnings of the risks that the indiscriminate and increasing use of pesticides poses to the environment and its biodiversity.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4135569','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4135569"><span>Recombinogenic Telomeres in Diploid Sorex granarius (Soricidae, Eulipotyphla) Fibroblast Cells</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Draskovic, I.; Minina, J. M.; Karamysheva, T. V.; Novo, C. L.; Liu, W.-Y.; Porreca, R. M.; Gibaud, A.; Zvereva, M. E.; Skvortsov, D. A.; Rubtsov, N. B.</p>
<p>2014-01-01</p>
<p>The telomere structure in the Iberian shrew Sorex granarius is characterized by unique, striking features, with short arms of acrocentric chromosomes carrying extremely long telomeres (up to 300 kb) with interspersed ribosomal DNA (rDNA) repeat blocks. In this work, we investigated the telomere physiology of S. granarius fibroblast cells and found that telomere repeats are transcribed on both strands and that there is no telomere-dependent senescence mechanism. Although telomerase activity is detectable throughout cell culture and appears to act on both short and long telomeres, we also discovered that signatures of a recombinogenic activity are omnipresent, including telomere-sister chromatid exchanges, formation of alternative lengthening of telomeres (ALT)-associated PML-like bodies, production of telomere circles, and a high frequency of telomeres carrying marks of a DNA damage response. Our results suggest that recombination participates in the maintenance of the very long telomeres in normal S. granarius fibroblasts. We discuss the possible interplay between the interspersed telomere and rDNA repeats in the stabilization of the very long telomeres in this organism. PMID:24842907</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19188697','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19188697"><span>Telomere length maintenance--an ALTernative mechanism.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Royle, N J; Foxon, J; Jeyapalan, J N; Mendez-Bermudez, A; Novo, C L; Williams, J; Cotton, V E</p>
<p>2008-01-01</p>
<p>The Alternative Lengthening of Telomeres (ALT) mechanism is utilised by approximately 10% of human tumours and a higher proportion of some types of sarcomas. ALT+ cell lines and tumours show heterogeneous telomere length, extra-chromosomal circular and linear telomeric DNA, ALT associated promyelocytic bodies (APBs), a high frequency of post-replication exchanges in telomeres (designated as telomere-sister chromatid exchanges, T-SCE) and high instability at a GC-rich minisatellite, MS32 (D1S8). It is clear that there is a link between the minisatellite instability and the mechanism that underpins ALT, however currently the nature of this relationship is uncertain. Single molecule analysis of telomeric DNA from ALT+ cell lines and tumours has revealed complex telomere mutations that have not been seen in cell lines or tumours that express telomerase. These complex telomere mutations cannot be explained by T-SCE but must arise by another inter-molecular process. The break-induced replication (BIR) model that may explain the observed high frequency of T-SCE and the presence of complex telomere mutations is reviewed. Copyright 2008 S. Karger AG, Basel.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/12547397','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/12547397"><span>Budding yeast mms4 is epistatic with rad52 and the function of Mms4 can be replaced by a bacterial Holliday junction resolvase.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Odagiri, Nao; Seki, Masayuki; Onoda, Fumitoshi; Yoshimura, Akari; Watanabe, Sei; Enomoto, Takemi</p>
<p>2003-03-01</p>
<p>MMS4 of Saccharomyces cerevisiae was originally identified as the gene responsible for one of the collection of methyl methanesulfonate (MMS)-sensitive mutants, mms4. Recently it was identified as a synthetic lethal gene with an SGS1 mutation. Epistatic analyses revealed that MMS4 is involved in a pathway leading to homologous recombination requiring Rad52 or in the recombination itself, in which SGS1 is also involved. MMS sensitivity of mms4 but not sgs1, was suppressed by introducing a bacterial Holliday junction (HJ) resolvase, RusA. The frequencies of spontaneously occurring unequal sister chromatid recombination (SCR) and loss of marker in the rDNA in haploid mms4 cells and interchromosomal recombination between heteroalleles in diploid mms4 cells were essentially the same as those of wild-type cells. Although UV- and MMS-induced interchromosomal recombination was defective in sgs1 diploid cells, hyper-induction of interchromosomal recombination was observed in diploid mms4 cells, indicating that the function of Mms4 is dispensable for this type of recombination.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17020097','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17020097"><span>[Cytogenetic effects of low dose radiation with different LET in human peripheral blood lymphocytes and possible mechanisms of their realization].</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Nasonova, E A; Shmakova, N L; Komova, O V; Mel'nikova, L A; Fadeeva, T A; Krasavin, E A</p>
<p>2006-01-01</p>
<p>The induction of chromosome damage by the exposure to low doses of gamma-(60)Co and accelerated carbon ions 12C in peripheral blood lymphocytes of different donors was investigated. The complex nonlinear dose-effect dependence at the range from 1 to 50-70 cGy was observed. At the doses of 1-5 cGy the cells show the highest radiosensitivity (hypersensitivity), mainly due to the chromatid-type aberration, which is typical to those spontaneously generated in the cell and believed not to be induced by the irradiation of unstimulated lymphocytes according to the classical theory of aberration formation. With the increasing dose the frequency of the aberrations decreases significantly, in some cases up to the control level. At the doses over 50-70 cGy the dose-effect curve becomes linear. The possible role of the oxidative stress, caused by radiation-induced increase in mitochondrial reactive oxigen species (ROS) release in the phenomenon of hypersensitivity (HS) at low doses is discussed as well as cytoprotective mechanisms causing the increased radioresistance at higher doses.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/10189155','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/10189155"><span>Sister chromatid exchange analysis in workers exposed to noise and vibration.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Silva, M J; Carothers, A; Castelo Branco, N A; Dias, A; Boavida, M G</p>
<p>1999-03-01</p>
<p>There has been a growing interest in the combined effects of noise and vibration. In a population of aeronautical workers diagnosed with vibroacoustic disease (VAD), a large incidence of malignancy was detected. These workers were exposed to large pressure amplitude (LPA) (> or = 90 dB SPL) noise, with energy content concentrated within the low frequency (LF) bands (< or = 500 Hz) and whole-body vibration (WBV). To our knowledge, there are no studies conducted in humans or animals that address the issue of the potential genotoxic effects of vibration combined with noise. In the present study, the levels of sister chromatid exchanges (SCE) and of cells with high frequencies of SCE (HFC) were analyzed in peripheral blood lymphocytes of workers employed in various occupations within the aeronautical industry. SCE and HFC were analyzed in lymphocytes of 50 workers occupationally exposed to noise and vibration and of 34 office-worker controls (G0). The exposed group included: 10 hand-vibrating tool operators (G1), 15 engine test cell technicians (G2), 12 aircraft run-up technicians (G3) and 13 Portuguese Air Force helicopter pilots (G4). Groups 2-4 were exposed to WBV and LPALF noise; group 1 was exposed to LPA high frequency noise and local vibration. Statistical analysis of the mean SCE count per cell was carried out by multiple regression analysis comparing various predictor variables: type of exposure, duration of exposure, age, and cigarette consumption. Only cigarette consumption and type of exposure were found to be significantly correlated with the mean SCE frequency. After allowing for the effects of smoking, the analysis indicates that: 1) there was no significant difference between G1 and G0 (p > 0.05); 2) the differences between G2 and G0, G3 and G0, G4 and G0 were all highly significant (p < 0.001); 3) there was no significant difference between G2 and G3 (p > 0.05), nor between G2 and G3 combined and G4 (p > 0.05); and 4) G2 and G4 combined had a significantly elevated mean SCE frequency compared G0 (p < 0.001). Statistical analysis of the proportion of HFC was consistent with these results. Our data suggest that occupational exposure to LPALF noise and WBV may lead to increased levels of SCE in men. These results also suggest a reason for the high incidence of malignancy in VAD patients. The observed effects may not reflect a direct action of these physical agents on DNA. Alternative explanations may lie in the noise-, vibration-, and/or stress-induced pathophysiological changes.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3951935','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3951935"><span>Mechanism, Prevalence, and More Severe Neuropathy Phenotype of the Charcot-Marie-Tooth Type 1A Triplication</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Liu, Pengfei; Gelowani, Violet; Zhang, Feng; Drory, Vivian E.; Ben-Shachar, Shay; Roney, Erin; Medeiros, Adam C.; Moore, Rebecca J.; DiVincenzo, Christina; Burnette, William B.; Higgins, Joseph J.; Li, Jun; Orr-Urtreger, Avi; Lupski, James R.</p>
<p>2014-01-01</p>
<p>Copy-number variations cause genomic disorders. Triplications, unlike deletions and duplications, are poorly understood because of challenges in molecular identification, the choice of a proper model system for study, and awareness of their phenotypic consequences. We investigated the genomic disorder Charcot-Marie-Tooth disease type 1A (CMT1A), a dominant peripheral neuropathy caused by a 1.4 Mb recurrent duplication occurring by nonallelic homologous recombination. We identified CMT1A triplications in families in which the duplication segregates. The triplications arose de novo from maternally transmitted duplications and caused a more severe distal symmetric polyneuropathy phenotype. The recombination that generated the triplication occurred between sister chromatids on the duplication-bearing chromosome and could accompany gene conversions with the homologous chromosome. Diagnostic testing for CMT1A (n = 20,661 individuals) identified 13% (n = 2,752 individuals) with duplication and 0.024% (n = 5 individuals) with segmental tetrasomy, suggesting that triplications emerge from duplications at a rate as high as ∼1:550, which is more frequent than the rate of de novo duplication. We propose that individuals with duplications are predisposed to acquiring triplications and that the population prevalence of triplication is underascertained. PMID:24530202</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2928865','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2928865"><span>Topoisomerase IIα maintains genomic stability through decatenation G2 checkpoint signaling</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Bower, Jacquelyn J.; Karaca, Gamze F.; Zhou, Yingchun; Simpson, Dennis A.; Cordeiro-Stone, Marila; Kaufmann, William K.</p>
<p>2010-01-01</p>
<p>Topoisomerase IIα (topoIIα) is an essential mammalian enzyme that topologically modifies DNA and is required for chromosome segregation during mitosis. Previous research suggests that inhibition of topoII decatenatory activity triggers a G2 checkpoint response, which delays mitotic entry due to insufficient decatenation of daughter chromatids. Here we examine the effects of both topoIIα and topoIIβ on decatenatory activity in cell extracts, DNA damage and decatenation G2 checkpoint function, and the frequencies of p16INK4A allele loss and gain. In diploid human fibroblast lines, depletion of topoIIα by siRNA was associated with severely reduced decatenatory activity, delayed progression from G2 into mitosis, and insensitivity to G2 arrest induced by the topoII catalytic inhibitor ICRF-193. Furthermore, interphase nuclei of topoIIα-depleted cells displayed increased frequencies of losses and gains of the tumor suppressor genetic locus p16INK4A. This study demonstrates that the topoIIα protein is required for decatenation G2 checkpoint function, and inactivation of decatenation and the decatenation G2 checkpoint leads to abnormal chromosome segregation and genomic instability. PMID:20562910</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11313115','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11313115"><span>Genotoxicity of dill (Anethum graveolens L.), peppermint (Menthaxpiperita L.) and pine (Pinus sylvestris L.) essential oils in human lymphocytes and Drosophila melanogaster.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Lazutka, J R; Mierauskiene, J; Slapsyte, G; Dedonyte, V</p>
<p>2001-05-01</p>
<p>Genotoxic properties of the essential oils extracted from dill (Anethum graveolens L.) herb and seeds, peppermint (Menthaxpiperita L.) herb and pine (Pinus sylvestris L.) needles were studied using chromosome aberration (CA) and sister chromatid exchange (SCE) tests in human lymphocytes in vitro, and Drosophila melanogaster somatic mutation and recombination test (SMART) in vivo. In the CA test, the most active essential oil was from dill seeds, then followed essential oils from dill herb, peppermint herb and pine needles, respectively. In the SCE test, the most active essential oils were from dill herb and seeds followed by essential oils from pine needles and peppermint herb. Essential oils from dill herb and seeds and pine needles induced CA and SCE in a clear dose-dependent manner, while peppermint essential oil induced SCE in a dose-independent manner. All essential oils were cytotoxic for human lymphocytes. In the SMART test, a dose-dependent increase in mutation frequency was observed for essential oils from pine and dill herb. Peppermint essential oil induced mutations in a dose-independent manner. Essential oil from dill seeds was almost inactive in the SMART test.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/12444553','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/12444553"><span>Expression of hpttg proto-oncogene in lymphoid neoplasias.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Sáez, Carmen; Pereda, Teresa; Borrero, Juan J; Espina, Agueda; Romero, Francisco; Tortolero, María; Pintor-Toro, José A; Segura, Dolores I; Japón, Miguel A</p>
<p>2002-11-21</p>
<p>Pituitary tumor-transforming gene (pttg) is a distinct proto-oncogene which is expressed in certain normal tissues with high proliferation rate and in a variety of tumors. PTTG is the vertebrate analog of yeast securins Pds1 and Cut2 with a key role in the regulation of sister chromatid separation during mitosis. Impairment of PTTG regulated functions is expected to lead to chromosomal instability and aneuploidy. Human pttg (hpttg) is abundantly expressed in Jurkat T lymphoblastic lymphoma cells but not in normal peripheral blood leukocytes. To obtain additional data on the potential role of hpttg in lymphomagenesis we selected 150 cases of lymphoid tumors for the assessment of hpttg expression in tumor tissues. Immunohistochemical studies on formalin-fixed, paraffin-embedded tissues revealed hPTTG in 38.8% of B-cell lymphomas, 70.2% of T-cell lymphomas, and 73.1% of Hodgkin's lymphomas. Among B-cell lymphomas, the most frequently immunostained tumors were plasma cell tumors, diffuse large cell lymphomas, and follicle center cell lymphomas. In Hodgkin's disease, immunoreactivity was mainly noted in Reed-Sternberg cells. In conclusion, the frequent overexpression of hpttg in many histological subtypes of lymphoma suggests the involvement of this proto-oncogene in lymphomagenesis.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23764456','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23764456"><span>Modulation of radiation-induced and mitomycin C-induced chromosome damage by apigenin in human lymphocytes in vitro.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Sharma, Narinder K</p>
<p>2013-09-01</p>
<p>Apigenin (APG), a flavone, is known to exhibit antioxidant, antimutagenic and antitumorigenic activity, both in vivo and in vitro. The aim of this study is to investigate the modulatory effects of APG on human lymphocytes after irradiation with gamma rays (3 Gy) or treatment with the antineoplastic agent, mitomycin C (MMC), in vitro. Cytogenetic biomarkers such as chromosome aberrations (CAs), sister chromatid exchanges (SCEs) and cytochalasin-B blocked micronuclei (CBMN), were studied in blood lymphocytes treated with radiation, or antineoplastic agent (MMC), and APG. Whole blood lymphocytes were cultured in vitro using a standard protocol. No significant differences were found in the frequency of CAs or micronuclei (MN) in human peripheral blood lymphocytes irradiated with gamma rays (3 Gy) and then post-treated with APG. There was an increase in the frequency of SCEs per cell in APG-treated samples compared with the controls. Lymphocytes treated with MMC in the presence of APG exhibited a significant decrease (P < 0.01) in the frequency of SCEs compared with MMC treatment alone. The data for the MN test indicated that APG treatment significantly reduced (P < 0.01) the frequency of MMC-induced MN.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3766282','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3766282"><span>Modulation of radiation-induced and mitomycin C-induced chromosome damage by apigenin in human lymphocytes in vitro</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Sharma, Narinder K.</p>
<p>2013-01-01</p>
<p>Apigenin (APG), a flavone, is known to exhibit antioxidant, antimutagenic and antitumorigenic activity, both in vivo and in vitro. The aim of this study is to investigate the modulatory effects of APG on human lymphocytes after irradiation with gamma rays (3 Gy) or treatment with the antineoplastic agent, mitomycin C (MMC), in vitro. Cytogenetic biomarkers such as chromosome aberrations (CAs), sister chromatid exchanges (SCEs) and cytochalasin-B blocked micronuclei (CBMN), were studied in blood lymphocytes treated with radiation, or antineoplastic agent (MMC), and APG. Whole blood lymphocytes were cultured in vitro using a standard protocol. No significant differences were found in the frequency of CAs or micronuclei (MN) in human peripheral blood lymphocytes irradiated with gamma rays (3 Gy) and then post-treated with APG. There was an increase in the frequency of SCEs per cell in APG-treated samples compared with the controls. Lymphocytes treated with MMC in the presence of APG exhibited a significant decrease (P < 0.01) in the frequency of SCEs compared with MMC treatment alone. The data for the MN test indicated that APG treatment significantly reduced (P < 0.01) the frequency of MMC-induced MN. PMID:23764456</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20231364','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20231364"><span>RecQL5 promotes genome stabilization through two parallel mechanisms--interacting with RNA polymerase II and acting as a helicase.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Islam, M Nurul; Fox, David; Guo, Rong; Enomoto, Takemi; Wang, Weidong</p>
<p>2010-05-01</p>
<p>The RecQL5 helicase is essential for maintaining genome stability and reducing cancer risk. To elucidate its mechanism of action, we purified a RecQL5-associated complex and identified its major component as RNA polymerase II (Pol II). Bioinformatics and structural modeling-guided mutagenesis revealed two conserved regions in RecQL5 as KIX and SRI domains, already known in transcriptional regulators for Pol II. The RecQL5-KIX domain binds both initiation (Pol IIa) and elongation (Pol IIo) forms of the polymerase, whereas the RecQL5-SRI domain interacts only with the elongation form. Fully functional RecQL5 requires both helicase activity and associations with the initiation polymerase, because mutants lacking either activity are partially defective in the suppression of sister chromatid exchange and resistance to camptothecin-induced DNA damage, and mutants lacking both activities are completely defective. We propose that RecQL5 promotes genome stabilization through two parallel mechanisms: by participation in homologous recombination-dependent DNA repair as a RecQ helicase and by regulating the initiation of Pol II to reduce transcription-associated replication impairment and recombination.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4758955','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4758955"><span>Cohesin-interacting protein WAPL-1 regulates meiotic chromosome structure and cohesion by antagonizing specific cohesin complexes</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Crawley, Oliver; Barroso, Consuelo; Testori, Sarah; Ferrandiz, Nuria; Silva, Nicola; Castellano-Pozo, Maikel; Jaso-Tamame, Angel Luis; Martinez-Perez, Enrique</p>
<p>2016-01-01</p>
<p>Wapl induces cohesin dissociation from DNA throughout the mitotic cell cycle, modulating sister chromatid cohesion and higher-order chromatin structure. Cohesin complexes containing meiosis-specific kleisin subunits govern most aspects of meiotic chromosome function, but whether Wapl regulates these complexes remains unknown. We show that during C. elegans oogenesis WAPL-1 antagonizes binding of cohesin containing COH-3/4 kleisins, but not REC-8, demonstrating that sensitivity to WAPL-1 is dictated by kleisin identity. By restricting the amount of chromosome-associated COH-3/4 cohesin, WAPL-1 controls chromosome structure throughout meiotic prophase. In the absence of REC-8, WAPL-1 inhibits COH-3/4-mediated cohesion, which requires crossover-fated events formed during meiotic recombination. Thus, WAPL-1 promotes functional specialization of meiotic cohesin: WAPL-1-sensitive COH-3/4 complexes modulate higher-order chromosome structure, while WAPL-1-refractory REC-8 complexes provide stable cohesion. Surprisingly, a WAPL-1-independent mechanism removes cohesin before metaphase I. Our studies provide insight into how meiosis-specific cohesin complexes are regulated to ensure formation of euploid gametes. DOI: http://dx.doi.org/10.7554/eLife.10851.001 PMID:26841696</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/6657895-ntp-report-toxicity-studies-ethylbenzene-f344-rats-b6c3f1-mice-inhalation-studies-report-march-june','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/6657895-ntp-report-toxicity-studies-ethylbenzene-f344-rats-b6c3f1-mice-inhalation-studies-report-march-june"><span>Ntp report on the toxicity studies of ethylbenzene in f344/n rats and b6c3f1 mice (inhalation studies). Report for 29 March-30 June 1988</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Chan, P.</p>
<p>1992-03-01</p>
<p>Inhalation toxicology studies of ethylbenzene (99% pure) were conducted by exposing groups of F344/N rats and B6C3F1 mice of each sex to ethylbenzene vapor at chamber concentrations of 0 to 1000 ppm, 6 hours per day, 5 days per week for 13 weeks. No rats or mice died during the 13-week exposure. Body weight gains were slightly lower in the high dose groups of male and female rats, but the differences were not statistically significant. Absolute and relative kidney, liver, and lung weights were increased in the exposed rats, while weight increases occurred only in the livers of exposed mice.more » No changes were observed in the evaluation of sperm or vaginal cytology in rats or mice. Ethylbenzene was not mutagenic in Salmonella and did not induce chromosomal aberrations or sister chromatid exchanges in Chinese hamster ovary (CHO) cells in vitro, though it did induce trifluorothymidine resistance in mouse lymphoma cells at the highest concentration tested. Micronuclei assays in peripheral blood of mice were negative.« less</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11752236','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11752236"><span>Chromosomal rearrangements involving telomeric DNA sequences in Balb/3T3 cells transfected with the Ha-ras oncogene.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Peitl, Paulo; Mello, Stephano S; Camparoto, Marjori L; Passos, Geraldo A S; Hande, Manoor P; Cardoso, Renato S; Sakamoto-Hojo, Elza T</p>
<p>2002-01-01</p>
<p>Chromosomal instability involving telomeric DNA sequences was studied in mouse Balb/3T3 fibroblasts transfected with a mutated human c-Ha-ras-1 gene (B61 cells) and spontaneously immortalized normal parental cells (A31 cells), using fluorescence in situ hybridization (FISH). FISH analysis with a telomeric probe revealed high frequencies of chromosome alterations involving telomeric regions, mainly stable and unstable Robertsonian fusion-like configurations (RLC) (0.25 and 1.95/cell in A31 and B61 cells, respectively) and chromosome ends lacking telomeric signals in one (LTS') or both chromatids (LTS") (5.9 and 17.5/cell for A31 and B61 cells, respectively). Interstitial telomeric sequences (ITS) were also detected at both non-telomeric sites and in the centromeres of RLC. The frequencies of RLCs with ITS located in the centromeres were 3-fold higher in B61 compared with A31 cells. We demonstrated a high level of chromosome instability involving telomeric DNA sequences in ras-transfected cells overexpressing ras mRNA, which could be a consequence of rapid cell cycle progression associated with a deficient telomere capping mechanism.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/6641592-preliminary-study-effects-military-obscurant-smokes-flora-fauna-during-field-laboratory-exposures-final-technical-report','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/6641592-preliminary-study-effects-military-obscurant-smokes-flora-fauna-during-field-laboratory-exposures-final-technical-report"><span>Preliminary study of effects of military obscurant smokes on flora and fauna during field and laboratory exposures. Final technical report</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Schaeffer, D.J.; Lower, W.R.; Kapila, S.</p>
<p>1986-12-01</p>
<p>Since continued routine use of obscurant smokes could be detrimental to the native flora and fauna of training sites, a preliminary biological and chemical study of smokes was conducted to determine whether tests could be developed to demonstrate measurable changes in organisms exposed to smokes and to evaluate whether short exposures to smokes produced measurable changes in the organisms tested. Fog oil, hexachloroethane, and tank diesel smokes were tested. Tradescantia clones were examined for mutagenic effects indicated by micronuclei induction in developing pollen and pink somatic mutations in stamen hairs. Photosynthetic perturbations were measured in Tradescantia and Ambrosia dumosa usingmore » variable fluorescence induction. Animals were examined for sister chromatid exchanges and chromosome aberrations. It was found that all of the smokes tested exerted varying degrees of physiological and mutagenic effects in one or several of the assay systems at one or more of the exposure distances. These studies indicate that exposed ecological systems, or at least components of these systems, are at a higher risk than are control organisms for several types of damage attributed to obscurant smoke exposure.« less</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4357872','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4357872"><span>Different autosomes evolved into sex chromosomes in the sister genera of Salix and Populus</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Hou, Jing; Ye, Ning; Zhang, Defang; Chen, Yingnan; Fang, Lecheng; Dai, Xiaogang; Yin, Tongming</p>
<p>2015-01-01</p>
<p>Willows (Salix) and poplars (Populus) are dioecious plants in Salicaceae family. Sex chromosome in poplar genome was consistently reported to be associated with chromosome XIX. In contrast to poplar, this study revealed that chromosome XV was sex chromosome in willow. Previous studies revealed that both ZZ/ZW and XX/XY sex-determining systems could be present in some species of Populus. In this study, sex of S. suchowensis was found to be determined by the ZW system in which the female was the heterogametic gender. Gene syntenic and collinear comparisons revealed macrosynteny between sex chromosomes and the corresponding autosomes between these two lineages. By contrast, no syntenic segments were found to be shared between poplar's and willow's sex chromosomes. Syntenic analysis also revealed substantial chromosome rearrangements between willow's alternate sex chromatids. Since willow and poplar originate from a common ancestor, we proposed that evolution of autosomes into sex chromosomes in these two lineages occurred after their divergence. Results of this study indicate that sex chromosomes in Salicaceae are still at the early stage of evolutionary divergence. Additionally, this study provided valuable information for better understanding the genetics and evolution of sex chromosome in dioecious plants. PMID:25766834</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2893158','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2893158"><span>MAPK-Activated Protein Kinase 2 Is Required for Mouse Meiotic Spindle Assembly and Kinetochore-Microtubule Attachment</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Qi, Shu-Tao; Tong, Jing-Shan; Wei, Liang; Li, Mo; Ouyang, Ying-Chun; Hou, Yi; Schatten, Heide; Sun, Qing-Yuan</p>
<p>2010-01-01</p>
<p>MAPK-activated protein kinase 2 (MK2), a direct substrate of p38 MAPK, plays key roles in multiple physiological functions in mitosis. Here, we show for the first time the unique distribution pattern of MK2 in meiosis. Phospho-MK2 was localized on bipolar spindle minus ends and along the interstitial axes of homologous chromosomes extending over centromere regions and arm regions at metaphase of first meiosis (MI stage) in mouse oocytes. At metaphase of second meiosis (MII stage), p-MK2 was localized on the bipolar spindle minus ends and at the inner centromere region of sister chromatids as dots. Knockdown or inhibition of MK2 resulted in spindle defects. Spindles were surrounded by irregular nondisjunction chromosomes, which were arranged in an amphitelic or syntelic/monotelic manner, or chromosomes detached from the spindles. Kinetochore–microtubule attachments were impaired in MK2-deficient oocytes because spindle microtubules became unstable in response to cold treatment. In addition, homologous chromosome segregation and meiosis progression were inhibited in these oocytes. Our data suggest that MK2 may be essential for functional meiotic bipolar spindle formation, chromosome segregation and proper kinetochore–microtubule attachments. PMID:20596525</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28220956','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28220956"><span>Releasing the cohesin ring: A rigid scaffold model for opening the DNA exit gate by Pds5 and Wapl.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Ouyang, Zhuqing; Yu, Hongtao</p>
<p>2017-04-01</p>
<p>The ring-shaped ATPase machine, cohesin, regulates sister chromatid cohesion, transcription, and DNA repair by topologically entrapping DNA. Here, we propose a rigid scaffold model to explain how the cohesin regulators Pds5 and Wapl release cohesin from chromosomes. Recent studies have established the Smc3-Scc1 interface as the DNA exit gate of cohesin, revealed a requirement for ATP hydrolysis in ring opening, suggested regulation of the cohesin ATPase activity by DNA and Smc3 acetylation, and provided insights into how Pds5 and Wapl open this exit gate. We hypothesize that Pds5, Wapl, and SA1/2 form a rigid scaffold that docks on Scc1 and anchors the N-terminal domain of Scc1 (Scc1N) to the Smc1 ATPase head. Relative movements between the Smc1-3 ATPase heads driven by ATP and Wapl disrupt the Smc3-Scc1 interface. Pds5 binds the dissociated Scc1N and prolongs this open state of cohesin, releasing DNA. We review the evidence supporting this model and suggest experiments that can further test its key principles. © 2017 WILEY Periodicals, Inc.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19665797','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19665797"><span>Genotoxic biomonitoring of agricultural workers exposed to pesticides in the north of Sinaloa State, Mexico.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Martínez-Valenzuela, Carmen; Gómez-Arroyo, Sandra; Villalobos-Pietrini, Rafael; Waliszewski, Stefan; Calderón-Segura, María Elena; Félix-Gastélum, Rubén; Alvarez-Torres, Armando</p>
<p>2009-11-01</p>
<p>Genotoxic damage was evaluated in 70 agricultural workers, 25 women and 45 men, exposed to pesticides in Las Grullas, Ahome, Sinaloa, Mexico, with an average of 7 years of exposure. The effect was detected through the sister chromatid exchanges (SCE) in lymphocytes of peripheral blood and micronuclei (MN) and other nuclear anomalies (NA) in buccal exfoliated cells. Also, the influence on cellular proliferation kinetics (CPK) was studied by means of the replication index (RI) and the cytotoxic effect was examined with the mitotic index (MI). The non-exposed group consisted of 70 other persons, 21 women and 47 men from the city of Los Mochis, Sinaloa, Mexico. Significant differences between the exposed and the non-exposed groups were observed in SCE, CPK, MI, MN and NA. Analysis of variance revealed that age, gender, smoking and alcohol consumption did not have a significant effect on genetic damage. However, there was a correlation between exposure time to pesticides and SCE frequency. These results could have been due to the exposure of workers to pesticides containing different chemical compounds. This study afforded valuable data to estimate the possible risk to health associated with pesticide exposure.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29905781','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29905781"><span>Association between genomic instability and evolutionary chromosomal rearrangements in Neotropical Primates.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Puntieri, Fiona; Andrioli, Nancy B; Nieves, Mariela</p>
<p>2018-06-14</p>
<p>During the last decades the mammalian genome has been proposed to have regions prone to breakage and reorganization concentrated in certain chromosomal bands that seem to correspond to evolutionary breakpoints. These bands are likely to be involved in chromosome fragility or instability. In Primates, some biomarkers of genetic damage may be associated with various degrees of genomic instability. Here, we investigated the usefulness of Sister Chromatid Exchange (SCE) as a biomarker of potential sites of frequent chromosome breakage and rearrangement in Alouatta caraya, Ateles chamek, Ateles paniscus and Cebus cay. These Neotropical species have particular genomic and chromosomal features allowing the analysis of genomic instability for comparative purposes. We determined the frequency of spontaneous induction of SCEs and assessed the relationship between these and structural rearrangements implicated in the evolution of the primates of interest. Overall, A. caraya and C. cay presented a low proportion of statistically significant unstable bands, suggesting fairly stable genomes and the existence of some kind of protection against endogenous damage. In contrast, Ateles showed a highly significant proportion of unstable bands; these were mainly found in the rearranged regions, which is consistent with the numerous genomic reorganizations that might have occurred during the evolution of this genus.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3263857','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3263857"><span>ASURA (PHB2) Is Required for Kinetochore Assembly and Subsequent Chromosome Congression</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Lee, Mei Hann; Lin, Linyen; Equilibrina, Ilma; Uchiyama, Susumu; Matsunaga, Sachihiro; Fukui, Kiichi</p>
<p>2011-01-01</p>
<p>ASURA (PHB2) knockdown has been known to cause premature loss of sister chromatid cohesion, and disrupt the localization of several outer plate proteins to the kinetochore. As a result, cells are arrested at mitotic phase and chromosomes fail to congress to the metaphase plate. In this study, we further clarified the mechanism underlying ASURA function on chromosome congression. Interestingly, ASURA is not specifically localized at the kinetochore during mitotic phase, unlike other kinetochore proteins which construct the kinetochore. Electron microscopy (EM) observation showed that ASURA is required for proper kinetochore formation. By the partial depletion of ASURA, kinetochore maturation is impaired, and kinetochores showing fibrillar balls without a well-defined outer plates are often observed. Moreover, even when the outer plates of kinetochores are constructed, most showed structures stretched and/or distended from the centromere, which resembled premature kinetochores at prometaphase, indicating that the constructed kinetochore plates are less rigid against tension derived from kinetochore microtubule pulling forces. We concluded that ASURA is an essential protein for complete kinetochore development, although ASURA is not being integrated to the kinetochore. These results highlight the uniqueness of ASURA as a kinetochore protein. PMID:22282585</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4974335','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4974335"><span>The Clathrin-dependent Spindle Proteome*</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Rao, Sushma R.; Flores-Rodriguez, Neftali; Page, Scott L.; Wong, Chin; Robinson, Phillip J.; Chircop, Megan</p>
<p>2016-01-01</p>
<p>The mitotic spindle is required for chromosome congression and subsequent equal segregation of sister chromatids. These processes involve a complex network of signaling molecules located at the spindle. The endocytic protein, clathrin, has a “moonlighting” role during mitosis, whereby it stabilizes the mitotic spindle. The signaling pathways that clathrin participates in to achieve mitotic spindle stability are unknown. Here, we assessed the mitotic spindle proteome and phosphoproteome in clathrin-depleted cells using quantitative MS/MS (data are available via ProteomeXchange with identifier PXD001603). We report a spindle proteome that consists of 3046 proteins and a spindle phosphoproteome consisting of 5157 phosphosites in 1641 phosphoproteins. Of these, 2908 (95.4%) proteins and 1636 (99.7%) phosphoproteins are known or predicted spindle-associated proteins. Clathrin-depletion from spindles resulted in dysregulation of 121 proteins and perturbed signaling to 47 phosphosites. The majority of these proteins increased in mitotic spindle abundance and six of these were validated by immunofluorescence microscopy. Functional pathway analysis confirmed the reported role of clathrin in mitotic spindle stabilization for chromosome alignment and highlighted possible new mechanisms of clathrin action. The data also revealed a novel second mitotic role for clathrin in bipolar spindle formation. PMID:27174698</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27174698','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27174698"><span>The Clathrin-dependent Spindle Proteome.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Rao, Sushma R; Flores-Rodriguez, Neftali; Page, Scott L; Wong, Chin; Robinson, Phillip J; Chircop, Megan</p>
<p>2016-08-01</p>
<p>The mitotic spindle is required for chromosome congression and subsequent equal segregation of sister chromatids. These processes involve a complex network of signaling molecules located at the spindle. The endocytic protein, clathrin, has a "moonlighting" role during mitosis, whereby it stabilizes the mitotic spindle. The signaling pathways that clathrin participates in to achieve mitotic spindle stability are unknown. Here, we assessed the mitotic spindle proteome and phosphoproteome in clathrin-depleted cells using quantitative MS/MS (data are available via ProteomeXchange with identifier PXD001603). We report a spindle proteome that consists of 3046 proteins and a spindle phosphoproteome consisting of 5157 phosphosites in 1641 phosphoproteins. Of these, 2908 (95.4%) proteins and 1636 (99.7%) phosphoproteins are known or predicted spindle-associated proteins. Clathrin-depletion from spindles resulted in dysregulation of 121 proteins and perturbed signaling to 47 phosphosites. The majority of these proteins increased in mitotic spindle abundance and six of these were validated by immunofluorescence microscopy. Functional pathway analysis confirmed the reported role of clathrin in mitotic spindle stabilization for chromosome alignment and highlighted possible new mechanisms of clathrin action. The data also revealed a novel second mitotic role for clathrin in bipolar spindle formation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('http://hdl.handle.net/2060/19870016464','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/19870016464"><span>Genetic toxicity studies of organic chemicals found as contaminants in spacecraft cabin atmospheres</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p>
<p>Torres, Joseph, Jr.</p>
<p>1987-01-01</p>
<p>Astronauts can be exposed during spaceflight to organic chemical contaminants in the spacecraft cabin atmosphere. Toxic exposures may cause lesions in the cellular DNA which are subsequently expressed as sister-chromatid exchanges (SCE). Analysis of SCE is a sensitive short term assay techinque to detect and quantitate exposures to DNA damaging (mutagenic) substances. The increase in SCE incidence over baseline (control) levels is generally proportional to the concentration of the mutagen and to the duration of exposure. The BHK-21 baby hamster kidney cell line was the in vitro test system used. Test organics were added to the culture media for 18 hrs, in concentrations ranging from one to 20 ppm. Acetaldehyde and carbon disulfide were chosen for this study since they have occurred as atmospheric contaminants in many of the STS flights, and have been reported to have toxic and mutagenic effects in various test systems. Glutaraldehyde was chosen because few data are available on the mutagenicity of this common fixative, which is carried on STS flights for use in biological experiments. Acetaldehyde was a very strong inducer of SCE at concentrations of 2 ppm and above. Glutaraldehyde and carbon disulfide failed to induce SCE.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=19860021961&hterms=Organic+Chemical&qs=N%3D0%26Ntk%3DAll%26Ntx%3Dmode%2Bmatchall%26Ntt%3DOrganic%2BChemical','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=19860021961&hterms=Organic+Chemical&qs=N%3D0%26Ntk%3DAll%26Ntx%3Dmode%2Bmatchall%26Ntt%3DOrganic%2BChemical"><span>In vitro cytogenetic studies of organic chemicals found as contaminants in spacecraft cabin atmospheres</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p>
<p>Torres, J.</p>
<p>1986-01-01</p>
<p>Astronauts can be exposed during spaceflight to organic chemical contaminants in the spacecraft cabin atmosphere. Toxic exposures may cause lesions in the cellular DNA which are subsequently expressed as sister-chromatid exchanges (SCE). Analysis of SCE is a sensitive short-term assay technique to detect and quantitate exposures to DNA-damaging (mutagenic) substances. The increase in SCE incidence over baseline (control) levels is generally proportional to the concentration of the mutagen and to the duration of exposure. Dichloromethane (methylene chloride) was chosen for this study since it occurred as an atmospheric contaminant in ten of the first 12 STS flights, and has been reported to have toxic and mutagenic effects in various test systems. Glutaraldehyde was chosen because relatively few data are available on the toxicity or mutagenicity of this common biological fixative, which is carried on STS flights for use in biological experiments. The BHK-21 baby hamster kidney cell line was the in vitro test system used in this study. Neither dichloromethane (10 ppm to 500 ppm) nor glutaraldehyde (1 ppm to 10 ppm) increased SCE levels following 20-hour exposure of BHK-21 cells to the test chemicals.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19863290','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19863290"><span>Chromosome instability on children with asthma.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Lialiaris, Theodore; Polyzou, Aggeliki; Mpountoukas, Panagiotis; Tsiggene, Anthi; Kouskoukis, Alexandros; Pouliliou, Stamatia; Paraskakis, Emmanouil; Tentes, Ioannis; Trypsianis, Grigorios; Chatzimichail, Athanasios</p>
<p>2009-10-01</p>
<p>Asthma is a complex disease with multiple interactions between genetic and environmental factors. The aim of our study was to investigate the possible genetic instability in asthmatic patients (AP) with asthma in human cultured peripheral blood lymphocytes. Furthermore, the presence of either cytostaticity or cytotoxicity was demonstrated. Human peripheral blood lymphocytes were cultured from 18 admitted children to the Pediatric Clinic of the University Hospital of Alexandroupolis (average age 7.2 years), and 9 healthy blood donors were used as control subjects (average age 6.5 years), none of whom was receiving drugs for medical or other reasons. A significant (p < 0.05) increase in spontaneous sister chromatid exchanges (SCEs) frequency in asthmatic patients compared with control subjects was observed. No statistically significant modification in the spontaneous proliferation rate index (PRI) in AP compared with the controls was demonstrated. Finally, MMC induced a statistically significant increase in SCEs frequency both to controls and to AP, with the MMC-induced SCEs rates in AP being statistically (p < 0.01) higher compared to the MMC-induced SCEs in controls. We try to improve a new diagnostic process of possible genetic instability by a combination of genotoxic, cytostatic and cytotoxic effects of asthma on human peripheral lymphocytes.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24187132','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24187132"><span>Phosphorylation of microtubule-binding protein Hec1 by mitotic kinase Aurora B specifies spindle checkpoint kinase Mps1 signaling at the kinetochore.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Zhu, Tongge; Dou, Zhen; Qin, Bo; Jin, Changjiang; Wang, Xinghui; Xu, Leilei; Wang, Zhaoyang; Zhu, Lijuan; Liu, Fusheng; Gao, Xinjiao; Ke, Yuwen; Wang, Zhiyong; Aikhionbare, Felix; Fu, Chuanhai; Ding, Xia; Yao, Xuebiao</p>
<p>2013-12-13</p>
<p>The spindle assembly checkpoint (SAC) is a quality control device to ensure accurate chromosome attachment to spindle microtubule for equal segregation of sister chromatid. Aurora B is essential for SAC function by sensing chromosome bi-orientation via spatial regulation of kinetochore substrates. However, it has remained elusive as to how Aurora B couples kinetochore-microtubule attachment to SAC signaling. Here, we show that Hec1 interacts with Mps1 and specifies its kinetochore localization via its calponin homology (CH) domain and N-terminal 80 amino acids. Interestingly, phosphorylation of the Hec1 by Aurora B weakens its interaction with microtubules but promotes Hec1 binding to Mps1. Significantly, the temporal regulation of Hec1 phosphorylation orchestrates kinetochore-microtubule attachment and Mps1 loading to the kinetochore. Persistent expression of phosphomimetic Hec1 mutant induces a hyperactivation of SAC, suggesting that phosphorylation-elicited Hec1 conformational change is used as a switch to orchestrate SAC activation to concurrent destabilization of aberrant kinetochore attachment. Taken together, these results define a novel role for Aurora B-Hec1-Mps1 signaling axis in governing accurate chromosome segregation in mitosis.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3861662','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3861662"><span>Phosphorylation of Microtubule-binding Protein Hec1 by Mitotic Kinase Aurora B Specifies Spindle Checkpoint Kinase Mps1 Signaling at the Kinetochore*</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Zhu, Tongge; Dou, Zhen; Qin, Bo; Jin, Changjiang; Wang, Xinghui; Xu, Leilei; Wang, Zhaoyang; Zhu, Lijuan; Liu, Fusheng; Gao, Xinjiao; Ke, Yuwen; Wang, Zhiyong; Aikhionbare, Felix; Fu, Chuanhai; Ding, Xia; Yao, Xuebiao</p>
<p>2013-01-01</p>
<p>The spindle assembly checkpoint (SAC) is a quality control device to ensure accurate chromosome attachment to spindle microtubule for equal segregation of sister chromatid. Aurora B is essential for SAC function by sensing chromosome bi-orientation via spatial regulation of kinetochore substrates. However, it has remained elusive as to how Aurora B couples kinetochore-microtubule attachment to SAC signaling. Here, we show that Hec1 interacts with Mps1 and specifies its kinetochore localization via its calponin homology (CH) domain and N-terminal 80 amino acids. Interestingly, phosphorylation of the Hec1 by Aurora B weakens its interaction with microtubules but promotes Hec1 binding to Mps1. Significantly, the temporal regulation of Hec1 phosphorylation orchestrates kinetochore-microtubule attachment and Mps1 loading to the kinetochore. Persistent expression of phosphomimetic Hec1 mutant induces a hyperactivation of SAC, suggesting that phosphorylation-elicited Hec1 conformational change is used as a switch to orchestrate SAC activation to concurrent destabilization of aberrant kinetochore attachment. Taken together, these results define a novel role for Aurora B-Hec1-Mps1 signaling axis in governing accurate chromosome segregation in mitosis. PMID:24187132</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1521169','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1521169"><span>Monitoring human exposure to urban air pollutants</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Barale, R.; Barrai, I.; Sbrana, I.; Migliore, L.; Marrazzini, A.; Scarcelli, V.; Bacci, E.; Di Sibio, A.; Tessa, A.; Cocchi, L.; Lubrano, V.; Vassalle, C.; He, J.</p>
<p>1993-01-01</p>
<p>A multidisciplinary study on a general population exposed to vehicle exhaust was undertaken in Pisa in 1991. Environmental factors such as air pollution and those associated with lifestyle were studied. Meanwhile, biological and medical indicators of health condition were investigated. Chromosomal aberrations, sister chromatid exchanges (SCEs), and micronuclei in lymphocytes were included for the assessment of the genotoxic risk. Because of the large number (3800) of subjects being investigated, standardization of protocols was compulsory. The results on data reproducibility are reported. To assess the reliability of the protocol on a large scale, the population of Porto Tolle, a village located in northeast Italy, was studied and compared to a subset of the Pisa population. Preliminary results showed that probable differences between the two populations and invididuals were present in terms of SCE frequencies. The study was potentially able to detect the effects of several factors such as age, smoking, genetics, and environment. The in vitro treatment of lymphocytes with diepoxybutane confirmed the presence of more responsive individuals and permitted us to investigate the genetic predisposition to genetic damage. The possible influence of environmental factors was studied by correlation analyses with external exposure to air pollutants as well as with several lifestyle factors. PMID:8143653</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/1800901','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/1800901"><span>The effects of pilocarpine nitrate upon the mitotic index of mouse bone marrow cells.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Prabhu, M P; Hegde, M J</p>
<p>1991-11-01</p>
<p>Aneuploidies are the most common chromosomal causes for spontaneous abortions and constitute a major part of genetic disorders among the neonates. Aneuploidy producing agents (aneugens) pose serious genetic hazards to the human population. Therefore, testing for aneuploidy induction should be part of the requirement in drug safety guidelines. The aneugenic potential of pilocarpine nitrate, an alkaloid drug used as an ophthalmic solution was screened by chromosome analysis studies in the bone marrow cells of mice. Using the technique developed by Miller and Adler (1989) we evaluated changes in the mitotic index (MI), induction of chromatid contraction and spreading (C-mitoses) and decrease of anaphase frequencies as indicators of the aneuploidy inducing potency of the drug. Concentrations of pilocarpine nitrate of 4, 8 and 12 mg/kg body weight were administered intraperitoneally to mice. Colchicine-treated and water-treated animals formed the positive and negative controls. The data obtained in the cytogenetic analysis of both dose-response and time-response studies showed a significant induction of C-mitotic effects in the mouse bone marrow. The positive results indicated that the drug is a potential aneugen and should be further evaluated.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=20050000480&hterms=yeast&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D10%26Ntt%3Dyeast','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=20050000480&hterms=yeast&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D10%26Ntt%3Dyeast"><span>Diploid yeast cells yield homozygous spontaneous mutations</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p>
<p>Esposito, M. S.; Bruschi, C. V.; Brushi, C. V. (Principal Investigator)</p>
<p>1993-01-01</p>
<p>A leucine-requiring hybrid of Saccharomyces cerevisiae, homoallelic at the LEU1 locus (leu1-12/leu1-12) and heterozygous for three chromosome-VII genetic markers distal to the LEU1 locus, was employed to inquire: (1) whether spontaneous gene mutation and mitotic segregation of heterozygous markers occur in positive nonrandom association and (2) whether homozygous LEU1/LEU1 mutant diploids are generated. The results demonstrate that gene mutation of leu1-12 to LEU1 and mitotic segregation of heterozygous chromosome-VII markers occur in strong positive nonrandom association, suggesting that the stimulatory DNA lesion is both mutagenic and recombinogenic. In addition, genetic analysis of diploid Leu+ revertants revealed that approximately 3% of mutations of leu1-12 to LEU1 result in LEU1/LEU1 homozygotes. Red-white sectored Leu+ colonies exhibit genotypes that implicate post-replicational chromatid breakage and exchange near the site of leu1-12 reversion, chromosome loss, and subsequent restitution of diploidy, in the sequence of events leading to mutational homozygosis. By analogy, diploid cell populations can yield variants homozygous for novel recessive gene mutations at biologically significant rates. Mutational homozygosis may be relevant to both carcinogenesis and the evolution of asexual diploid organisms.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/21043703-fission-yeast-dam1-a8-mutant-resistant-rescued-anti-microtubule-agent','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/21043703-fission-yeast-dam1-a8-mutant-resistant-rescued-anti-microtubule-agent"><span>Fission yeast dam1-A8 mutant is resistant to and rescued by an anti-microtubule agent</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Griffiths, Karen; Masuda, Hirohisa; Dhut, Susheela</p>
<p>2008-04-11</p>
<p>The Dam1/DASH outer kinetochore complex is required for high-fidelity chromosome segregation in budding and fission yeast. Unlike budding yeast, the fission yeast complex is non-essential, however it promotes bipolar microtubule attachment in conjunction with microtubule-depolymerising kinesin-8 Klp5 and Klp6. Here, we screened for dam1 temperature sensitive mutants in a klp5 null background and identified dam1-A8 that contains two amino acid substitutions in the C-terminus (H126R and E149G). dam1-A8klp5 mutant cells display massive chromosome missegregation with lagging chromosomes and monopolar attachment of sister chromatids to one SPB (spindle pole body). Unexpectedly contrary to a deletion mutant that is hypersensitive to microtubule-destabilisingmore » drugs, dam1-A8 is resistant and furthermore the temperature sensitivity of dam1-A8klp5 is rescued by addition of these drugs. This indicates that the hyper-stabilised rigidity of kinetochore-spindle mal-attachments is the primary cause of lethality. Our result shows that fine-tuning of Dam1 activity is essential for chromosome bi-orientation.« less</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5499779','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5499779"><span>The LSH/HELLS homolog Irc5 contributes to cohesin association with chromatin in yeast</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Bakowski, Tomasz; Maciaszczyk-Dziubinska, Ewa; Wysocki, Robert</p>
<p>2017-01-01</p>
<p>Abstract Accurate chromosome segregation is essential for every living cell as unequal distribution of chromosomes during cell division may result in genome instability that manifests in carcinogenesis and developmental disorders. Irc5 from Saccharomyces cerevisiae is a member of the conserved Snf2 family of ATP-dependent DNA translocases and its function is poorly understood. Here, we identify Irc5 as a novel interactor of the cohesin complex. Irc5 associates with Scc1 cohesin subunit and contributes to cohesin binding to chromatin. Disruption of IRC5 decreases cohesin levels at centromeres and chromosome arms, causing premature sister chromatid separation. Moreover, reduced cohesin occupancy at the rDNA region in cells lacking IRC5 leads to the loss of rDNA repeats. We also show that the translocase activity of Irc5 is required for its function in cohesion pathway. Finally, we demonstrate that in the absence of Irc5 both the level of chromatin-bound Scc2, a member of cohesin loading complex, and physical interaction between Scc1 and Scc2 are reduced. Our results suggest that Irc5 is an auxiliary factor that is involved in cohesin association with chromatin. PMID:28383696</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2002Natur.418..994H','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2002Natur.418..994H"><span>A chromatin remodelling complex that loads cohesin onto human chromosomes</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p>
<p>Hakimi, Mohamed-Ali; Bochar, Daniel A.; Schmiesing, John A.; Dong, Yuanshu; Barak, Orr G.; Speicher, David W.; Yokomori, Kyoko; Shiekhattar, Ramin</p>
<p>2002-08-01</p>
<p>Nucleosomal DNA is arranged in a higher-order structure that presents a barrier to most cellular processes involving protein DNA interactions. The cellular machinery involved in sister chromatid cohesion, the cohesin complex, also requires access to the nucleosomal DNA to perform its function in chromosome segregation. The machineries that provide this accessibility are termed chromatin remodelling factors. Here, we report the isolation of a human ISWI (SNF2h)-containing chromatin remodelling complex that encompasses components of the cohesin and NuRD complexes. We show that the hRAD21 subunit of the cohesin complex directly interacts with the ATPase subunit SNF2h. Mapping of hRAD21, SNF2h and Mi2 binding sites by chromatin immunoprecipitation experiments reveals the specific association of these three proteins with human DNA elements containing Alu sequences. We find a correlation between modification of histone tails and association of the SNF2h/cohesin complex with chromatin. Moreover, we show that the association of the cohesin complex with chromatin can be regulated by the state of DNA methylation. Finally, we present evidence pointing to a role for the ATPase activity of SNF2h in the loading of hRAD21 on chromatin.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2120196','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2120196"><span>ScII: an abundant chromosome scaffold protein is a member of a family of putative ATPases with an unusual predicted tertiary structure</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p></p>
<p>1994-01-01</p>
<p>Here, we describe the cloning and characterization of ScII, the second most abundant protein after topoisomerase II, of the chromosome scaffold fraction to be identified. ScII is structurally related to a protein, Smc1p, previously found to be required for accurate chromosome segregation in Saccharomyces cerevisiae. ScII and the other members of the emerging family of SMC1-like proteins are likely to be novel ATPases, with NTP-binding A and B sites separated by two lengthy regions predicted to form an alpha-helical coiled-coil. Analysis of the ScII B site predicted that ScII might use ATP by a mechanism similar to the bacterial recN DNA repair and recombination enzyme. ScII is a mitosis-specific scaffold protein that colocalizes with topoisomerase II in mitotic chromosomes. However, ScII appears not to be associated with the interphase nuclear matrix. ScII might thus play a role in mitotic processes such as chromosome condensation or sister chromatid disjunction, both of which have been previously shown to involve topoisomerase II. PMID:7929577</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26869222','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26869222"><span>Nuclear envelope expansion is crucial for proper chromosomal segregation during a closed mitosis.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Takemoto, Ai; Kawashima, Shigehiro A; Li, Juan-Juan; Jeffery, Linda; Yamatsugu, Kenzo; Elemento, Olivier; Nurse, Paul</p>
<p>2016-03-15</p>
<p>Here, we screened a 10,371 library of diverse molecules using a drug-sensitive fission yeast strain to identify compounds which cause defects in chromosome segregation during mitosis. We identified a phosphorium-ylide-based compound Cutin-1 which inhibits nuclear envelope expansion and nuclear elongation during the closed mitosis of fission yeast, and showed that its target is the β-subunit of fatty acid synthase. A point mutation in the dehydratase domain of Fas1 conferred in vivo and in vitro resistance to Cutin-1. Time-lapse photomicrography showed that the bulk of the chromosomes were only transiently separated during mitosis, and nucleoli separation was defective. Subsequently sister chromatids re-associated leading to chromosomal mis-segregation. These segregation defects were reduced when the nuclear volume was increased and were increased when the nuclear volume was reduced. We propose that there needs to be sufficient nuclear volume to allow the nuclear elongation necessary during a closed mitosis to take place for proper chromosome segregation, and that inhibition of fatty acid synthase compromises nuclear elongation and leads to defects in chromosomal segregation. © 2016. Published by The Company of Biologists Ltd.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17982445','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17982445"><span>Telomere lengthening early in development.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Liu, Lin; Bailey, Susan M; Okuka, Maja; Muñoz, Purificación; Li, Chao; Zhou, Lingjun; Wu, Chao; Czerwiec, Eva; Sandler, Laurel; Seyfang, Andreas; Blasco, Maria A; Keefe, David L</p>
<p>2007-12-01</p>
<p>Stem cells and cancer cells maintain telomere length mostly through telomerase. Telomerase activity is high in male germ line and stem cells, but is low or absent in mature oocytes and cleavage stage embryos, and then high again in blastocysts. How early embryos reset telomere length remains poorly understood. Here, we show that oocytes actually have shorter telomeres than somatic cells, but their telomeres lengthen remarkably during early cleavage development. Moreover, parthenogenetically activated oocytes also lengthen their telomeres, thus the capacity to elongate telomeres must reside within oocytes themselves. Notably, telomeres also elongate in the early cleavage embryos of telomerase-null mice, demonstrating that telomerase is unlikely to be responsible for the abrupt lengthening of telomeres in these cells. Coincident with telomere lengthening, extensive telomere sister-chromatid exchange (T-SCE) and colocalization of the DNA recombination proteins Rad50 and TRF1 were observed in early cleavage embryos. Both T-SCE and DNA recombination proteins decrease in blastocyst stage embryos, whereas telomerase activity increases and telomeres elongate only slowly. We suggest that telomeres lengthen during the early cleavage cycles following fertilization through a recombination-based mechanism, and that from the blastocyst stage onwards, telomerase only maintains the telomere length established by this alternative mechanism.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25993311','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25993311"><span>Casein Kinase 1 and Phosphorylation of Cohesin Subunit Rec11 (SA3) Promote Meiotic Recombination through Linear Element Formation.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Phadnis, Naina; Cipak, Lubos; Polakova, Silvia; Hyppa, Randy W; Cipakova, Ingrid; Anrather, Dorothea; Karvaiova, Lucia; Mechtler, Karl; Smith, Gerald R; Gregan, Juraj</p>
<p>2015-05-01</p>
<p>Proper meiotic chromosome segregation, essential for sexual reproduction, requires timely formation and removal of sister chromatid cohesion and crossing-over between homologs. Early in meiosis cohesins hold sisters together and also promote formation of DNA double-strand breaks, obligate precursors to crossovers. Later, cohesin cleavage allows chromosome segregation. We show that in fission yeast redundant casein kinase 1 homologs, Hhp1 and Hhp2, previously shown to regulate segregation via phosphorylation of the Rec8 cohesin subunit, are also required for high-level meiotic DNA breakage and recombination. Unexpectedly, these kinases also mediate phosphorylation of a different meiosis-specific cohesin subunit Rec11. This phosphorylation in turn leads to loading of linear element proteins Rec10 and Rec27, related to synaptonemal complex proteins of other species, and thereby promotes DNA breakage and recombination. Our results provide novel insights into the regulation of chromosomal features required for crossing-over and successful reproduction. The mammalian functional homolog of Rec11 (STAG3) is also phosphorylated during meiosis and appears to be required for fertility, indicating wide conservation of the meiotic events reported here.</p>
</li>
</ol>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5510351','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5510351"><span>Sordaria, a model system to uncover links between meiotic pairing and recombination</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Zickler, Denise; Espagne, Eric</p>
<p>2017-01-01</p>
<p>The mycelial fungus Sordaria macrospora was first used as experimental system for meiotic recombination. This review shows that it provides also a powerful cytological system for dissecting chromosome dynamics in wild-type and mutant meioses. Fundamental cytogenetic findings include: (1) The identification of presynaptic alignment as a key step in pairing of homologous chromosomes. (2) The discovery that biochemical complexes that mediate recombination at the DNA level concomitantly mediate pairing of homologs. (3) This pairing process involves not only resolution but also avoidance of chromosomal entanglements and the resolution system includes dissolution of constraining DNA recombination interactions, achieved by a unique role of Mlh1. (4) Discovery that the central components of the synaptonemal complex directly mediate the re-localization of the recombination proteins from on-axis to in-between homologue axis positions. (5) Identification of putative STUbL protein Hei10 as a structure-based signal transduction molecule that coordinates progression and differentiation of recombinational interactions at multiple stages. (6) Discovery that a single interference process mediates both nucleation of the SC and designation of crossover sites, thereby ensuring even spacing of both features. (7) Discovery of local modulation of sister-chromatid cohesion at sites of crossover recombination. PMID:26877138</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3561757','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3561757"><span>Discovering non-random segregation of sister chromatids: the naïve treatment of a premature discovery</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Lark, Karl G.</p>
<p>2013-01-01</p>
<p>The discovery of non-random chromosome segregation (Figure 1) is discussed from the perspective of what was known in 1965 and 1966. The distinction between daughter, parent, or grandparent strands of DNA was developed in a bacterial system and led to the discovery that multiple copies of DNA elements of bacteria are not distributed randomly with respect to the age of the template strand. Experiments with higher eukaryotic cells demonstrated that during mitosis Mendel’s laws were violated; and the initial serendipitous choice of eukaryotic cell system led to the striking example of non-random segregation of parent and grandparent DNA template strands in primary cultures of cells derived from mouse embryos. Attempts to extrapolate these findings to established tissue culture lines demonstrated that the property could be lost. Experiments using plant root tips demonstrated that the phenomenon exists in plants and that it was, at some level, under genetic control. Despite publication in major journals and symposia (Lark et al., 1966, 1967; Lark, 1967, 1969a,b,c) the potential implications of these findings were ignored for several decades. Here we explore possible reasons for the pre-maturity (Stent, 1972) of this discovery. PMID:23378946</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/5176634-mutagens-cooked-foods-metabolism-genetic-toxicity','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/5176634-mutagens-cooked-foods-metabolism-genetic-toxicity"><span>Mutagens in cooked foods - metabolism and genetic toxicity</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Felton, J.S.; Bjeldanes, L.F.; Hatch, F.T.</p>
<p>1984-02-17</p>
<p>Recently developed in our laboratories is an efficient extraction procedure incorporating XAD resin adsorption which yields from 200/sup 0/C grilled ground beef an extract containing 230 Salmonella TA1538 revertants per g fresh weight of original ground beef. These mutagenic components are specific for frameshift-sensitive Salmonella strains and have an absolute requirement for metabolic activation. Normal-phase HPLC separation of methanol-extractable metabolites generated from reaction of 2-amino-3-methylimidazo (4,5-f)quinoline (IQ), a mutagenic component of broiled food with rat liver microsomes resulted in one direct-acting mutagenic peak and a second more polar peak still requiring metabolic activation. Two potent thermally-produced bacterial mutagens, 3-amino-1-methyl-5H-pyrido (4,3-b)more » indole (Trp-P-2) and IQ, were examined in mammalian cells. In excision repair-deficient CHO cells, Trp-P-2 exposure caused cytotoxicity, mutagenicity, sister chromatid exchange, and chromosomal aberrations at concentrations more than 30-fold lower than those for IQ. In normal repair-proficient CHO cells Trp-P-2 was one-half as active and IQ was inactive. Relative to Trp-P-2, IQ is much more potent in the Salmonella bacterial system than in mammalian CHO cells.« less</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21811037','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21811037"><span>Lack of genotoxicity in medical oncology nurses handling antineoplastic drugs: effect of work environment and protective equipment.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Gulten, Tuna; Evke, Elif; Ercan, Ilker; Evrensel, Turkkan; Kurt, Ender; Manavoglu, Osman</p>
<p>2011-01-01</p>
<p>In this study we aimed to investigate the genotoxic effects of antineoplastic agents in occupationally exposed oncology nurses. Genotoxic effects mean the disruptive effects in the integrity of DNA and they are associated with cancer development. Biomonitoring of health care workers handling antineoplastic agents is helpful for the evaluation of exposure to cytostatics. The study included an exposed and two control groups. The exposed group (n=9) was comprised of oncology nurses. The first (n=9) and second (n=10) control groups were comprised of subjects who did not come into contact with antineoplastic drugs working respectively in the same department with oncology nurses and in different departments. Genotoxicity evaluation was performed using SCE analysis. After applying culture, harvest and chromosome staining procedures, a total of 25 metaphases were analyzed per person. Kruskal Wallis test was used to perform statistical analysis. A statistically significant difference of sister chromatid exchange frequencies was not observed between the exposed and control groups. Lack of genotoxicity in medical oncology nurses might be due to good working conditions with high standards of technical equipment and improved personal protection.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22593209','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22593209"><span>RTEL1 contributes to DNA replication and repair and telomere maintenance.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Uringa, Evert-Jan; Lisaingo, Kathleen; Pickett, Hilda A; Brind'Amour, Julie; Rohde, Jan-Hendrik; Zelensky, Alex; Essers, Jeroen; Lansdorp, Peter M</p>
<p>2012-07-01</p>
<p>Telomere maintenance and DNA repair are important processes that protect the genome against instability. mRtel1, an essential helicase, is a dominant factor setting telomere length in mice. In addition, mRtel1 is involved in DNA double-strand break repair. The role of mRtel1 in telomere maintenance and genome stability is poorly understood. Therefore we used mRtel1-deficient mouse embryonic stem cells to examine the function of mRtel1 in replication, DNA repair, recombination, and telomere maintenance. mRtel1-deficient mouse embryonic stem cells showed sensitivity to a range of DNA-damaging agents, highlighting its role in replication and genome maintenance. Deletion of mRtel1 increased the frequency of sister chromatid exchange events and suppressed gene replacement, demonstrating the involvement of the protein in homologous recombination. mRtel1 localized transiently at telomeres and is needed for efficient telomere replication. Of interest, in the absence of mRtel1, telomeres in embryonic stem cells appeared relatively stable in length, suggesting that mRtel1 is required to allow extension by telomerase. We propose that mRtel1 is a key protein for DNA replication, recombination, and repair and efficient elongation of telomeres by telomerase.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26716824','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26716824"><span>Analysis of the Possible Persistent Genotoxic Damage in Workers Linked to the Ardystil Syndrome.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Montoro, Alegria; Sebastià, Natividad; Hervás, David; Esteban, Valentín; Bonafont, Jose; Barquinero, Joan Francesc; Almonacid, Miguel; Cervera, Jose; Such, Esperanza; Verdú, Gumersindo; Soriano, José Miguel; Villaescusa, Juan Ignacio</p>
<p>2016-02-01</p>
<p>A combination of several factors including a change in the paint application system; a lack of proper hygiene; and inadequate safety measures caused a severe health impact in the workers of some textile painting factories. This outbreak, mainly characterized by respiratory disorders, caused the death of six people and it has been classified as Ardystil syndrome. Fifty-two workers involved in the outbreak and 48 healthy subjects not known to have exposed to the potentially mutagenic agents participated in the study. The program evaluated possible genotoxic damage through the sister chromatid exchange (SCE) cytogenetic biomarker assay. We determined the frequency of SCE, high-frequency cells (HFCs), and a ratio, which can be considered as a new parameter, allowing for the study of the SCE distribution pattern among the chromosomes. There was no statistically significant difference in the SCE frequency and in the mean number of HFCs between the control and the Ardystil-affected groups. However, smoking increased the incidence of all parameters studied in both the case and control groups. This study shows that workers involved in the Ardystil syndrome did not suffer genotoxic damage as measured by SCE and HFCs when compared with the control group.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3437562','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3437562"><span>Preparation and use of Xenopus egg extracts to study DNA replication and chromatin associated proteins</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Gillespie, Peter J.; Gambus, Agnieszka; Blow, J. Julian</p>
<p>2012-01-01</p>
<p>The use of cell-free extracts prepared from eggs of the South African clawed toad, Xenopus laevis, has led to many important discoveries in cell cycle research. These egg extracts recapitulate the key nuclear transitions of the eukaryotic cell cycle in vitro under apparently the same controls that exist in vivo. DNA added to the extract is first assembled into a nucleus and is then efficiently replicated. Progression of the extract into mitosis then allows the separation of paired sister chromatids. The Xenopus cell-free system is therefore uniquely suited to the study of the mechanisms, dynamics and integration of cell cycle regulated processes at a biochemical level. In this article we describe methods currently in use in our laboratory for the preparation of Xenopus egg extracts and demembranated sperm nuclei for the study of DNA replication in vitro. We also detail how DNA replication can be quantified in this system. In addition, we describe methods for isolating chromatin and chromatin-bound protein complexes from egg extracts. These recently developed and revised techniques provide a practical starting point for investigating the function of proteins involved in DNA replication. PMID:22521908</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1173145','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1173145"><span>ASCIZ regulates lesion-specific Rad51 focus formation and apoptosis after methylating DNA damage</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>McNees, Carolyn J; Conlan, Lindus A; Tenis, Nora; Heierhorst, Jörg</p>
<p>2005-01-01</p>
<p>Nuclear Rad51 focus formation is required for homology-directed repair of DNA double-strand breaks (DSBs), but its regulation in response to non-DSB lesions is poorly understood. Here we report a novel human SQ/TQ cluster domain-containing protein termed ASCIZ that forms Rad51-containing foci in response to base-modifying DNA methylating agents but not in response to DSB-inducing agents. ASCIZ foci seem to form prior to Rad51 recruitment, and an ASCIZ core domain can concentrate Rad51 in focus-like structures independently of DNA damage. ASCIZ depletion dramatically increases apoptosis after methylating DNA damage and impairs Rad51 focus formation in response to methylating agents but not after ionizing radiation. ASCIZ focus formation and increased apoptosis in ASCIZ-depleted cells depend on the mismatch repair protein MLH1. Interestingly, ASCIZ foci form efficiently during G1 phase, when sister chromatids are unavailable as recombination templates. We propose that ASCIZ acts as a lesion-specific focus scaffold in a Rad51-dependent pathway that resolves cytotoxic repair intermediates, most likely single-stranded DNA gaps, resulting from MLH1-dependent processing of base lesions. PMID:15933716</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/15933716','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/15933716"><span>ASCIZ regulates lesion-specific Rad51 focus formation and apoptosis after methylating DNA damage.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>McNees, Carolyn J; Conlan, Lindus A; Tenis, Nora; Heierhorst, Jörg</p>
<p>2005-07-06</p>
<p>Nuclear Rad51 focus formation is required for homology-directed repair of DNA double-strand breaks (DSBs), but its regulation in response to non-DSB lesions is poorly understood. Here we report a novel human SQ/TQ cluster domain-containing protein termed ASCIZ that forms Rad51-containing foci in response to base-modifying DNA methylating agents but not in response to DSB-inducing agents. ASCIZ foci seem to form prior to Rad51 recruitment, and an ASCIZ core domain can concentrate Rad51 in focus-like structures independently of DNA damage. ASCIZ depletion dramatically increases apoptosis after methylating DNA damage and impairs Rad51 focus formation in response to methylating agents but not after ionizing radiation. ASCIZ focus formation and increased apoptosis in ASCIZ-depleted cells depend on the mismatch repair protein MLH1. Interestingly, ASCIZ foci form efficiently during G1 phase, when sister chromatids are unavailable as recombination templates. We propose that ASCIZ acts as a lesion-specific focus scaffold in a Rad51-dependent pathway that resolves cytotoxic repair intermediates, most likely single-stranded DNA gaps, resulting from MLH1-dependent processing of base lesions.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/16730176','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/16730176"><span>Apollo, an Artemis-related nuclease, interacts with TRF2 and protects human telomeres in S phase.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>van Overbeek, Megan; de Lange, Titia</p>
<p>2006-07-11</p>
<p>Human chromosome ends are protected by shelterin, an abundant six-subunit protein complex that binds specifically to the telomeric-repeat sequences, regulates telomere length, and ensures that chromosome ends do not elicit a DNA-damage response (reviewed in). Using mass spectrometry of proteins associated with the shelterin component Rap1, we identified an SMN1/PSO2 nuclease family member that is closely related to Artemis. We refer to this protein as Apollo and report that Apollo has the ability to localize to telomeres through an interaction with the shelterin component TRF2. Although its low abundance at telomeres indicates that Apollo is not a core component of shelterin, Apollo knockdown with RNAi resulted in senescence and the activation of a DNA-damage signal at telomeres as evidenced by telomere-dysfunction-induced foci (TIFs). The TIFs occurred primarily in S phase, suggesting that Apollo contributes to a processing step associated with the replication of chromosome ends. Furthermore, some of the metaphase chromosomes showed two telomeric signals at single-chromatid ends, suggesting an aberrant telomere structure. We propose that the Artemis-like nuclease Apollo is a shelterin accessory factor required for the protection of telomeres during or after their replication.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20551906','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20551906"><span>SNMIB/Apollo protects leading-strand telomeres against NHEJ-mediated repair.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Lam, Yung C; Akhter, Shamima; Gu, Peili; Ye, Jing; Poulet, Anaïs; Giraud-Panis, Marie-Josèphe; Bailey, Susan M; Gilson, Eric; Legerski, Randy J; Chang, Sandy</p>
<p>2010-07-07</p>
<p>Progressive telomere attrition or deficiency of the protective shelterin complex elicits a DNA damage response as a result of a cell's inability to distinguish dysfunctional telomeric ends from DNA double-strand breaks. SNMIB/Apollo is a shelterin-associated protein and a member of the SMN1/PSO2 nuclease family that localizes to telomeres through its interaction with TRF2. Here, we generated SNMIB/Apollo knockout mouse embryo fibroblasts (MEFs) to probe the function of SNMIB/Apollo at mammalian telomeres. SNMIB/Apollo null MEFs exhibit an increased incidence of G2 chromatid-type fusions involving telomeres created by leading-strand DNA synthesis, reflective of a failure to protect these telomeres after DNA replication. Mutations within SNMIB/Apollo's conserved nuclease domain failed to suppress this phenotype, suggesting that its nuclease activity is required to protect leading-strand telomeres. SNMIB/Apollo(-/-)ATM(-/-) MEFs display robust telomere fusions when Trf2 is depleted, indicating that ATM is dispensable for repair of uncapped telomeres in this setting. Our data implicate the 5'-3' exonuclease function of SNM1B/Apollo in the generation of 3' single-stranded overhangs at newly replicated leading-strand telomeres to protect them from engaging the non-homologous end-joining pathway.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27998191','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27998191"><span>In vitro potential cytogenetic and oxidative stress effects of roxithromycin.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Arslan, Mehmet; Timocin, Taygun; Ila, Hasan B</p>
<p>2017-10-01</p>
<p>Macrolide antibiotic roxithromycin was evaluated in terms of its genotoxic, cytotoxic and oxidative stress effects. For this purpose; 25, 50, 100 and 200 μg/mL concentrations of roxithromycin were dissolved in dimethyl sulfoxide and treated to human peripheral blood lymphocytes for two different treatment periods (24 and 48 h). In chromosome aberration (CA) and micronucleus (MN) tests, roxithromycin did not show genotoxic effect. But it induced sister chromatid exchange (SCE) at the highest concentration (200 μg/mL) for the 24-h treatment period and at all concentrations (except 25 μg/mL) for the 48-h treatment period. Looking at cytotoxic effect of roxithromycin, statistically insignificant decreases on mitotic index and proliferation index were observed. Roxithromycin decreased nuclear division index (NDI) at highest two concentrations (100 and 200 μg/mL) for the 24-h treatment period and at all concentrations (expect 25 μg/mL) for the 48-h treatment period. Total oxidant values, total antioxidant values and oxidative stress index did not change with roxithromycin treatment. Eventually, roxithromycin did not have genotoxic and oxidative stress effects in human-cultured lymphocytes.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/18215246','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/18215246"><span>Chromosomal study of lettuce and its allied species (Lactuca spp., Asteraceae) by means of karyotype analysis and fluorescence in situ hybridization.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Matoba, Hideyuki; Mizutani, Takayuki; Nagano, Katsuya; Hoshi, Yoshikazu; Uchiyama, Hiroshi</p>
<p>2007-12-01</p>
<p>In this study, in addition to the karyotype analysis, the chromosomal distributions of 5 S and 18 S rDNAs, and the Arabidopsis-type (T3AG3) telomeric sequences were detected by means of fluorescence in situ hybridization (FISH) to promote the information of chromosomal organization and evolution in the cultivated lettuce and its wild relatives, L. sativa, L. serriola, L. saligna and L. virosa. The karyotype analysis revealed the dissimilarity between L. virosa and the remaining species. In all four Lactuca species studied, one 5 S rDNA and two 18 S rDNA loci were detected. The simultaneous FISH of 5 S and 18 S rDNAs revealed that both rDNA loci of L. sativa, L. serriola and L. saligna were identical, however, that of L. virosa was different from the other species. These analyses indicate the closer relationships between L. sativa/L. serriola and L. saligna rather than L. virosa. Arabidopsis-type telomeric sequences were detected at both ends of their chromatids of all chromosomes not in the other regions. This observation suggests the lack of telomere-mediated chromosomal rearrangements among the Lactuca chromosomes.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/2552405','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/2552405"><span>RADH, a gene of Saccharomyces cerevisiae encoding a putative DNA helicase involved in DNA repair. Characteristics of radH mutants and sequence of the gene.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Aboussekhra, A; Chanet, R; Zgaga, Z; Cassier-Chauvat, C; Heude, M; Fabre, F</p>
<p>1989-09-25</p>
<p>A new type of radiation-sensitive mutant of S. cerevisiae is described. The recessive radH mutation sensitizes to the lethal effect of UV radiations haploids in the G1 but not in the G2 mitotic phase. Homozygous diploids are as sensitive as G1 haploids. The UV-induced mutagenesis is depressed, while the induction of gene conversion is increased. The mutation is believed to channel the repair of lesions engaged in the mutagenic pathway into a recombination process, successful if the events involve sister-chromatids but lethal if they involve homologous chromosomes. The sequence of the RADH gene reveals that it may code for a DNA helicase, with a Mr of 134 kDa. All the consensus domains of known DNA helicases are present. Besides these consensus regions, strong homologies with the Rep and UvrD helicases of E. coli were found. The RadH putative helicase appears to belong to the set of proteins involved in the error-prone repair mechanism, at least for UV-induced lesions, and could act in coordination with the Rev3 error-prone DNA polymerase.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/1383801','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/1383801"><span>Effect of 60-Hz magnetic fields on ultraviolet light-induced mutation and mitotic recombination in Saccharomyces cerevisiae.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Ager, D D; Radul, J A</p>
<p>1992-12-01</p>
<p>The purpose of this study was to examine the effect of extremely low frequency (ELF) magnetic fields on the induction of genetic damage. In general, mutational studies involving ELF magnetic fields have proven negative. However, studies examining sister-chromatid exchange and chromosome aberrations have yielded conflicting results. In this study, we have examined whether 60-Hz magnetic fields are capable of inducing mutation or mitotic recombination in the yeast Saccharomyces cerevisiae. In addition we determined whether magnetic fields were capable of altering the genetic response of S. cerevisiae to UV (254 nm). We measured the frequencies of induced mutation, gene conversion and reciprocal mitotic crossing-over for exposures to magnetic fields alone (1 mT) or in combination with various UV exposures (2-50 J/m2). These experiments were performed using a repair-proficient strain (RAD+), as well as a strain of yeast (rad3) which is incapable of excising UV-induced thymine dimers. Magnetic field exposures did not induce mutation, gene conversion or reciprocal mitotic crossing-over in either of these strains, nor did the fields influence the frequencies of UV-induced genetic events.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4877051','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4877051"><span>Identification of Putative Mek1 Substrates during Meiosis in Saccharomyces cerevisiae Using Quantitative Phosphoproteomics</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Suhandynata, Raymond T.; Wan, Lihong; Zhou, Huilin; Hollingsworth, Nancy M.</p>
<p>2016-01-01</p>
<p>Meiotic recombination plays a key role in sexual reproduction as it generates crossovers that, in combination with sister chromatid cohesion, physically connect homologous chromosomes, thereby promoting their proper segregation at the first meiotic division. Meiotic recombination is initiated by programmed double strand breaks (DSBs) catalyzed by the evolutionarily conserved, topoisomerase-like protein Spo11. Repair of these DSBs is highly regulated to create crossovers between homologs that are distributed throughout the genome. This repair requires the presence of the mitotic recombinase, Rad51, as well as the strand exchange activity of the meiosis-specific recombinase, Dmc1. A key regulator of meiotic DSB repair in Saccharomyces cerevisiae is the meiosis-specific kinase Mek1, which promotes interhomolog strand invasion and is required for the meiotic recombination checkpoint and the crossover/noncrossover decision. Understanding how Mek1 regulates meiotic recombination requires the identification of its substrates. Towards that end, an unbiased phosphoproteomic approach utilizing Stable Isotope Labeling by Amino Acids in Cells (SILAC) was utilized to generate a list of potential Mek1 substrates, as well as proteins containing consensus phosphorylation sites for cyclin-dependent kinase, the checkpoint kinases, Mec1/Tel1, and the polo-like kinase, Cdc5. These experiments represent the first global phosphoproteomic dataset for proteins in meiotic budding yeast. PMID:27214570</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5333035','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5333035"><span>Links between DNA Replication, Stem Cells and Cancer</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Vassilev, Alex; DePamphilis, Melvin L.</p>
<p>2017-01-01</p>
<p>Cancers can be categorized into two groups: those whose frequency increases with age, and those resulting from errors during mammalian development. The first group is linked to DNA replication through the accumulation of genetic mutations that occur during proliferation of developmentally acquired stem cells that give rise to and maintain tissues and organs. These mutations, which result from DNA replication errors as well as environmental insults, fall into two categories; cancer driver mutations that initiate carcinogenesis and genome destabilizing mutations that promote aneuploidy through excess genome duplication and chromatid missegregation. Increased genome instability results in accelerated clonal evolution leading to the appearance of more aggressive clones with increased drug resistance. The second group of cancers, termed germ cell neoplasia, results from the mislocation of pluripotent stem cells during early development. During normal development, pluripotent stem cells that originate in early embryos give rise to all of the cell lineages in the embryo and adult, but when they mislocate to ectopic sites, they produce tumors. Remarkably, pluripotent stem cells, like many cancer cells, depend on the Geminin protein to prevent excess DNA replication from triggering DNA damage-dependent apoptosis. This link between the control of DNA replication during early development and germ cell neoplasia reveals Geminin as a potential chemotherapeutic target in the eradication of cancer progenitor cells. PMID:28125050</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2016PhRvE..93f2415J','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2016PhRvE..93f2415J"><span>Assembly of bipolar microtubule structures by passive cross-linkers and molecular motors</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p>
<p>Johann, D.; Goswami, D.; Kruse, K.</p>
<p>2016-06-01</p>
<p>During cell division, sister chromatids are segregated by the mitotic spindle, a bipolar assembly of interdigitating antiparallel polar filaments called microtubules. The spindle contains the midzone, a stable region of overlapping antiparallel microtubules, that is essential for maintaining bipolarity. Although a lot is known about the molecular players involved, the mechanism underlying midzone formation and maintenance is still poorly understood. We study the interaction of polar filaments that are cross-linked by molecular motors moving directionally and by passive cross-linkers diffusing along microtubules. Using a particle-based stochastic model, we find that the interplay of motors and passive cross-linkers can generate a stable finite overlap between a pair of antiparallel polar filaments. We develop a mean-field theory to study this mechanism in detail and investigate the influence of steric interactions between motors and passive cross-linkers on the overlap dynamics. In the presence of interspecies steric interactions, passive cross-linkers mimic the behavior of molecular motors and stable finite overlaps are generated even for non-cross-linking motors. Finally, we develop a mean-field theory for a bundle of aligned polar filaments and show that they can self-organize into a spindlelike pattern. Our work suggests possible ways as to how cells can generate spindle midzones and control their extensions.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28489060','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28489060"><span>The Effect of VPA on Increasing Radiosensitivity in Osteosarcoma Cells and Primary-Culture Cells from Chemical Carcinogen-Induced Breast Cancer in Rats.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Liu, Guochao; Wang, Hui; Zhang, Fengmei; Tian, Youjia; Tian, Zhujun; Cai, Zuchao; Lim, David; Feng, Zhihui</p>
<p>2017-05-10</p>
<p>This study explored whether valproic acid (VPA, a histone deacetylase inhibitor) could radiosensitize osteosarcoma and primary-culture tumor cells, and determined the mechanism of VPA-induced radiosensitization. The working system included osteosarcoma cells (U2OS) and primary-culture cells from chemical carcinogen (DMBA)-induced breast cancer in rats; and clonogenic survival, immunofluorescence, fluorescent in situ hybridization (FISH) for chromosome aberrations, and comet assays were used in this study. It was found that VPA at the safe or critical safe concentration of 0.5 or 1.0 mM VPA could result in the accumulation of more ionizing radiation (IR)-induced DNA double strand breaks, and increase the cell radiosensitivity. VPA-induced radiosensitivity was associated with the inhibition of DNA repair activity in the working systems. In addition, the chromosome aberrations including chromosome breaks, chromatid breaks, and radial structures significantly increased after the combination treatment of VPA and IR. Importantly, the results obtained by primary-culture cells from the tissue of chemical carcinogen-induced breast cancer in rats further confirmed our findings. The data in this study demonstrated that VPA at a safe dose was a radiosensitizer for osteosarcoma and primary-culture tumor cells through suppressing DNA-double strand breaks repair function.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5454939','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5454939"><span>The Effect of VPA on Increasing Radiosensitivity in Osteosarcoma Cells and Primary-Culture Cells from Chemical Carcinogen-Induced Breast Cancer in Rats</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Liu, Guochao; Wang, Hui; Zhang, Fengmei; Tian, Youjia; Tian, Zhujun; Cai, Zuchao; Lim, David; Feng, Zhihui</p>
<p>2017-01-01</p>
<p>This study explored whether valproic acid (VPA, a histone deacetylase inhibitor) could radiosensitize osteosarcoma and primary-culture tumor cells, and determined the mechanism of VPA-induced radiosensitization. The working system included osteosarcoma cells (U2OS) and primary-culture cells from chemical carcinogen (DMBA)-induced breast cancer in rats; and clonogenic survival, immunofluorescence, fluorescent in situ hybridization (FISH) for chromosome aberrations, and comet assays were used in this study. It was found that VPA at the safe or critical safe concentration of 0.5 or 1.0 mM VPA could result in the accumulation of more ionizing radiation (IR)-induced DNA double strand breaks, and increase the cell radiosensitivity. VPA-induced radiosensitivity was associated with the inhibition of DNA repair activity in the working systems. In addition, the chromosome aberrations including chromosome breaks, chromatid breaks, and radial structures significantly increased after the combination treatment of VPA and IR. Importantly, the results obtained by primary-culture cells from the tissue of chemical carcinogen-induced breast cancer in rats further confirmed our findings. The data in this study demonstrated that VPA at a safe dose was a radiosensitizer for osteosarcoma and primary-culture tumor cells through suppressing DNA-double strand breaks repair function. PMID:28489060</p>
</li>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2841330','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2841330"><span>GEN1/Yen1 and the SLX4 complex: solutions to the problem of Holliday junction resolution</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Svendsen, Jennifer M.; Harper, J. Wade</p>
<p>2010-01-01</p>
<p>Chromosomal double-strand breaks (DSBs) are considered to be among the most deleterious DNA lesions found in eukaryotic cells due to their propensity to promote genome instability. DSBs occur as a result of exogenous or endogenous DNA damage, and also occur during meiotic recombination. DSBs are often repaired through a process called homologous recombination (HR), which employs the sister chromatid in mitotic cells or the homologous chromosome in meiotic cells, as a template for repair. HR frequently involves the formation and resolution of four-way DNA structures referred to as the Holliday junction (HJ). Despite extensive study, the machinery and mechanisms used to process these structures in eukaryotes have remained poorly understood. Recent work has identified XPG and UvrC/GIY domain-containing structure-specific endonucleases that can symmetrically cleave HJs in vitro in a manner that allows for religation without additional processing, properties that are reminiscent of the classical RuvC HJ resolvase in bacteria. Genetic studies reveal potential roles for these HJ resolvases in repair after DNA damage and during meiosis. The stage is now set for a more comprehensive understanding of the specific roles these enzymes play in the response of cells to DSBs, collapsed replication forks, telomere dysfunction, and meiotic recombination. PMID:20203129</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=20040170285&hterms=Cancer&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D90%26Ntt%3DCancer','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=20040170285&hterms=Cancer&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D90%26Ntt%3DCancer"><span>Monitoring occupational exposure to cancer chemotherapy drugs</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p>
<p>Baker, E. S.; Connor, T. H.</p>
<p>1996-01-01</p>
<p>Reports of the health effects of handling cytotoxic drugs and compliance with guidelines for handling these agents are briefly reviewed, and studies using analytical and biological methods of detecting exposure are evaluated. There is little conclusive evidence of detrimental health effects from occupational exposure to cytotoxic drugs. Work practices have improved since the issuance of guidelines for handling these drugs, but compliance with the recommended practices is still inadequate. Of 64 reports published since 1979 on studies of workers' exposure to these drugs, 53 involved studies of changes in cellular or molecular endpoints (biological markers) and 12 described chemical analyses of drugs or their metabolites in urine (2 involved both, and 2 reported the same study). The primary biological markers used were urine mutagenicity, sister chromatid exchange, and chromosomal aberrations; other studies involved formation of micronuclei and measurements of urinary thioethers. The studies had small sample sizes, and the methods were qualitative, nonspecific, subject to many confounders, and possibly not sensitive enough to detect most occupational exposures. Since none of the currently available biological and analytical methods is sufficiently reliable or reproducible for routine monitoring of exposure in the workplace, further studies using these methods are not recommended; efforts should focus instead on wide-spread implementation of improved practices for handling cytotoxic drugs.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27851952','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27851952"><span>Shape Transformation of the Nuclear Envelope during Closed Mitosis.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Zhu, Qian; Zheng, Fan; Liu, Allen P; Qian, Jin; Fu, Chuanhai; Lin, Yuan</p>
<p>2016-11-15</p>
<p>The nuclear envelope (NE) in lower eukaryotes such as Schizosaccharomyces pombe undergoes large morphology changes during closed mitosis. However, which physical parameters are important in governing the shape evolution of the NE, and how defects in the dividing chromosomes/microtubules are reflected in those parameters, are fundamental questions that remain unresolved. In this study, we show that improper separation of chromosomes in genetically deficient cells leads to membrane tethering or asymmetric division in contrast to the formation of two equal-sized daughter nuclei in wild-type cells. We hypothesize that the poleward force is transmitted to the nuclear membrane through its physical contact with the separated sister chromatids at the two spindle poles. A theoretical model is developed to predict the morphology evolution of the NE where key factors such as the work done by the poleward force and bending and surface energies stored in the membrane have been taken into account. Interestingly, the predicted phase diagram, summarizing the dependence of nuclear shape on the size of the load transmission regions, and the pole-to-pole distance versus surface area relationship all quantitatively agree well with our experimental observations, suggesting that this model captures the essential physics involved in closed mitosis. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/6713508-ntp-technical-report-toxicity-studies-diethanolamine-cas-administered-topically-drinking-water-f344-rats-b6c3f1-mice-toxicity-report-series','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/6713508-ntp-technical-report-toxicity-studies-diethanolamine-cas-administered-topically-drinking-water-f344-rats-b6c3f1-mice-toxicity-report-series"><span>NTP technical report on toxicity studies of diethanolamine (CAS No. 111-42-2) administered topically and in drinking water to F344/n rats and B6C3F1 mice. Toxicity report series</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Melnick, R.L.</p>
<p>1992-10-01</p>
<p>Diethanolamine is a high-production chemical used in cosmetics, in cutting fluids, as a dispersing agent for agricultural chemicals, and as an absorbent for acidic gases. Toxicology studies of diethanolamine were conducted in F344/N rats and B6C3F1 mice of both sexes for 2 weeks (5/sex/species/dose) and 13 weeks (10/sex/species/dose) to characterize and compare the effects of oral and dermal exposure. In addition to histopathology, evaluations included clinical pathology, urinalyses, and sperm morphology or vaginal cytology. In vitro genetic toxicity studies included assessments of mutagenicity in Salmonella typhimurium and mouse lymphoma L5178Y cells, analysis of chromosomal aberrations and sister chromatid exchange inmore » Chinese hamster ovary cells, and determination of micronuclei formed in mice during the 13 week dermal exposure study. In the 13-week drinking water study in mice, nephropathy and tubular necrosis were observed in males, and degeneration of cardiac myocytes, and hepatocellular necrosis were seen in males and females. Cytologic alteration in the submandibular salivary gland was noted in male and female mice. Hepatocyte cytologic alteration also was noted in all dosed groups of mice.« less</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4620154','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4620154"><span>Atypical centromeres in plants—what they can tell us</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Cuacos, Maria; H. Franklin, F. Chris; Heckmann, Stefan</p>
<p>2015-01-01</p>
<p>The centromere, visible as the primary constriction of condensed metaphase chromosomes, is a defined chromosomal locus essential for genome stability. It mediates transient assembly of a multi-protein complex, the kinetochore, which enables interaction with spindle fibers and thus faithful segregation of the genetic information during nuclear divisions. Centromeric DNA varies in extent and sequence composition among organisms, but a common feature of almost all active eukaryotic centromeres is the presence of the centromeric histone H3 variant cenH3 (a.k.a. CENP-A). These typical centromere features apply to most studied species. However, a number of species display “atypical” centromeres, such as holocentromeres (centromere extension along almost the entire chromatid length) or neocentromeres (ectopic centromere activity). In this review, we provide an overview of different atypical centromere types found in plants including holocentromeres, de novo formed centromeres and terminal neocentromeres as well as di-, tri- and metapolycentromeres (more than one centromere per chromosomes). We discuss their specific and common features and compare them to centromere types found in other eukaryotic species. We also highlight new insights into centromere biology gained in plants with atypical centromeres such as distinct mechanisms to define a holocentromere, specific adaptations in species with holocentromeres during meiosis or various scenarios leading to neocentromere formation. PMID:26579160</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26579160','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26579160"><span>Atypical centromeres in plants-what they can tell us.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Cuacos, Maria; H Franklin, F Chris; Heckmann, Stefan</p>
<p>2015-01-01</p>
<p>The centromere, visible as the primary constriction of condensed metaphase chromosomes, is a defined chromosomal locus essential for genome stability. It mediates transient assembly of a multi-protein complex, the kinetochore, which enables interaction with spindle fibers and thus faithful segregation of the genetic information during nuclear divisions. Centromeric DNA varies in extent and sequence composition among organisms, but a common feature of almost all active eukaryotic centromeres is the presence of the centromeric histone H3 variant cenH3 (a.k.a. CENP-A). These typical centromere features apply to most studied species. However, a number of species display "atypical" centromeres, such as holocentromeres (centromere extension along almost the entire chromatid length) or neocentromeres (ectopic centromere activity). In this review, we provide an overview of different atypical centromere types found in plants including holocentromeres, de novo formed centromeres and terminal neocentromeres as well as di-, tri- and metapolycentromeres (more than one centromere per chromosomes). We discuss their specific and common features and compare them to centromere types found in other eukaryotic species. We also highlight new insights into centromere biology gained in plants with atypical centromeres such as distinct mechanisms to define a holocentromere, specific adaptations in species with holocentromeres during meiosis or various scenarios leading to neocentromere formation.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26124146','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26124146"><span>Arabidopsis MZT1 homologs GIP1 and GIP2 are essential for centromere architecture.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Batzenschlager, Morgane; Lermontova, Inna; Schubert, Veit; Fuchs, Jörg; Berr, Alexandre; Koini, Maria A; Houlné, Guy; Herzog, Etienne; Rutten, Twan; Alioua, Abdelmalek; Fransz, Paul; Schmit, Anne-Catherine; Chabouté, Marie-Edith</p>
<p>2015-07-14</p>
<p>Centromeres play a pivotal role in maintaining genome integrity by facilitating the recruitment of kinetochore and sister-chromatid cohesion proteins, both required for correct chromosome segregation. Centromeres are epigenetically specified by the presence of the histone H3 variant (CENH3). In this study, we investigate the role of the highly conserved γ-tubulin complex protein 3-interacting proteins (GIPs) in Arabidopsis centromere regulation. We show that GIPs form a complex with CENH3 in cycling cells. GIP depletion in the gip1gip2 knockdown mutant leads to a decreased CENH3 level at centromeres, despite a higher level of Mis18BP1/KNL2 present at both centromeric and ectopic sites. We thus postulate that GIPs are required to ensure CENH3 deposition and/or maintenance at centromeres. In addition, the recruitment at the centromere of other proteins such as the CENP-C kinetochore component and the cohesin subunit SMC3 is impaired in gip1gip2. These defects in centromere architecture result in aneuploidy due to severely altered centromeric cohesion. Altogether, we ascribe a central function to GIPs for the proper recruitment and/or stabilization of centromeric proteins essential in the specification of the centromere identity, as well as for centromeric cohesion in somatic cells.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26489653','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26489653"><span>Holocentromeres in Rhynchospora are associated with genome-wide centromere-specific repeat arrays interspersed among euchromatin.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Marques, André; Ribeiro, Tiago; Neumann, Pavel; Macas, Jiří; Novák, Petr; Schubert, Veit; Pellino, Marco; Fuchs, Jörg; Ma, Wei; Kuhlmann, Markus; Brandt, Ronny; Vanzela, André L L; Beseda, Tomáš; Šimková, Hana; Pedrosa-Harand, Andrea; Houben, Andreas</p>
<p>2015-11-03</p>
<p>Holocentric chromosomes lack a primary constriction, in contrast to monocentrics. They form kinetochores distributed along almost the entire poleward surface of the chromatids, to which spindle fibers attach. No centromere-specific DNA sequence has been found for any holocentric organism studied so far. It was proposed that centromeric repeats, typical for many monocentric species, could not occur in holocentrics, most likely because of differences in the centromere organization. Here we show that the holokinetic centromeres of the Cyperaceae Rhynchospora pubera are highly enriched by a centromeric histone H3 variant-interacting centromere-specific satellite family designated "Tyba" and by centromeric retrotransposons (i.e., CRRh) occurring as genome-wide interspersed arrays. Centromeric arrays vary in length from 3 to 16 kb and are intermingled with gene-coding sequences and transposable elements. We show that holocentromeres of metaphase chromosomes are composed of multiple centromeric units rather than possessing a diffuse organization, thus favoring the polycentric model. A cell-cycle-dependent shuffling of multiple centromeric units results in the formation of functional (poly)centromeres during mitosis. The genome-wide distribution of centromeric repeat arrays interspersing the euchromatin provides a previously unidentified type of centromeric chromatin organization among eukaryotes. Thus, different types of holocentromeres exist in different species, namely with and without centromeric repetitive sequences.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.osti.gov/biblio/21077779-occupational-exposure-antineoplastic-agents-induces-high-level-chromosome-damage-lack-effect-gst-polymorphisms','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/21077779-occupational-exposure-antineoplastic-agents-induces-high-level-chromosome-damage-lack-effect-gst-polymorphisms"><span>Occupational exposure to antineoplastic agents induces a high level of chromosome damage. Lack of an effect of GST polymorphisms</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p>
<p>Testa, Antonella; Giachelia, Manuela; Palma, Selena</p>
<p></p>
<p>The aim of our study was to investigate whether occupational exposure to antineoplastic drugs (AND) resulted in genetic damage, possibly indicative of adverse health effects in the long term. We performed a chromosomal aberrations (CA) analysis in peripheral blood lymphocytes (PBL) of a group of 76 trained nurses occupationally exposed to AND. Furthermore, we analysed whether genetic polymorphisms in four metabolic genes of the glutathione S-transferase (GST) family involved in antineoplastic drugs detoxification (GSTM1, GSTT1, GSTP1, GSTA1) had any effect on the yield of chromosomal aberrations in nurses exposed to antineoplastic agents. The exposed group showed a very significant increasemore » of genetic damage (p < 0.0001) potentially indicative of an increased risk of cancer. Unexpectedly, besides the elevated level of chromatid-type aberrations usually related to exposure to chemical agents, we found also severe chromosome damages such as chromosome deletions and dicentric chromosomes, usually related to radiation exposure. No significant association was detected between all GSTs genotypes and chromosome damage. In conclusion, our data show how the occupational exposure to AND is associated to a potential cancer risk, suggesting that current prevention methods do not completely eliminate opportunities for exposure and supporting the need to improve the actual safety practices.« less</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19365775','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19365775"><span>Exposure to bitumen fumes and genotoxic effects on Turkish asphalt workers.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Karaman, Ali; Pirim, Ibrahim</p>
<p>2009-04-01</p>
<p>Bitumen fumes consist essentially of polycyclic aromatic hydrocarbons (PAHs) and their derivatives, some of which are known to be carcinogenic or cocarcinogenic in humans. The aim of this study was to investigate exposure to asphalt fumes among Turkish asphalt workers and determine whether any effects could be detected with genotoxic tests. The study included 26 asphalt workers and 24 control subjects. Sister chromatid exchange (SCE) and micronucleus (MN) were determined in peripheral lymphocytes. Urinary 1-hydroxypyrene (1-OHP) excretion was used as a biomarker of occupational exposure to PAHs. The asphalt workers had a significant increase in SCEs and MN (for each, p < 0.001). A positive correlation existed between the duration of exposure and rates of SCE or MN frequencies (r = 0.49, p < 0.05; r = 0.53, p < 0.05, respectively). The concentration of 1-OHP in urine was higher for the asphalt workers than for the controls (p < 0.001). However, we found that there was no statistically significant correlation between the urinary 1-OHP concentration and SCEs or MN frequencies (r = 0.25, p > 0.5; r = 0.17, p > 0.5, respectively). This study shows that Turkish asphalt workers have an increased exposure to PAHs from bitumen fumes, and genotoxic effects could be detected by SCEs and MN tests.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25025061','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25025061"><span>Xanthium strumarium L. extracts produce DNA damage mediated by cytotoxicity in in vitro assays but does not induce micronucleus in mice.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Piloto Ferrer, Janet; Cozzi, Renata; Cornetta, Tommaso; Stano, Pasquale; Fiore, Mario; Degrassi, Francesca; De Salvia, Rosella; Remigio, Antonia; Francisco, Marbelis; Quiñones, Olga; Valdivia, Dayana; González, Maria L; Pérez, Carlos; Sánchez-Lamar, Angel</p>
<p>2014-01-01</p>
<p>Xanthium strumarium L. is a member of the Asteraceae commonly used in Cuba, mainly as diuretic. Some toxic properties of this plant have also been reported and, to date, very little is known about its genotoxic properties. The present work aims was to evaluate the potential cytotoxic and genotoxic risk of whole extract from Xanthium strumarium L. whole extract of aerial parts. No positive response was observed in a battery of four Salmonella typhimurium strains, when exposed to concentrations up to 5 mg/plate, with and without mammalian metabolic activation (liver microsomal S9 fraction from Wistar rats). In CHO cells, high concentrations (25-100 μg/mL) revealed significant reduction in cell viability. Results from sister chromatid exchanges, chromosome aberrations, and comet assay showed that X. strumarium extract is genotoxic at the highest concentration used, when clear cytotoxic effects were also observed. On the contrary, no increase in micronuclei frequency in bone marrow cells was observed when the extract was orally administered to mice (100, 500, and 2000 mg/Kg doses). The data presented here constitute the most complete study on the genotoxic potential of X. strumarium L. and show that the extract can induce in vitro DNA damage at cytotoxic concentrations.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4082875','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4082875"><span>Xanthium strumarium L. Extracts Produce DNA Damage Mediated by Cytotoxicity in In Vitro Assays but Does Not Induce Micronucleus in Mice</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Piloto Ferrer, Janet; Cozzi, Renata; Cornetta, Tommaso; Stano, Pasquale; Fiore, Mario; Degrassi, Francesca; De Salvia, Rosella; Remigio, Antonia; Francisco, Marbelis; Quiñones, Olga; Valdivia, Dayana; González, Maria L.; Pérez, Carlos; Sánchez-Lamar, Angel</p>
<p>2014-01-01</p>
<p>Xanthium strumarium L. is a member of the Asteraceae commonly used in Cuba, mainly as diuretic. Some toxic properties of this plant have also been reported and, to date, very little is known about its genotoxic properties. The present work aims was to evaluate the potential cytotoxic and genotoxic risk of whole extract from Xanthium strumarium L. whole extract of aerial parts. No positive response was observed in a battery of four Salmonella typhimurium strains, when exposed to concentrations up to 5 mg/plate, with and without mammalian metabolic activation (liver microsomal S9 fraction from Wistar rats). In CHO cells, high concentrations (25–100 μg/mL) revealed significant reduction in cell viability. Results from sister chromatid exchanges, chromosome aberrations, and comet assay showed that X. strumarium extract is genotoxic at the highest concentration used, when clear cytotoxic effects were also observed. On the contrary, no increase in micronuclei frequency in bone marrow cells was observed when the extract was orally administered to mice (100, 500, and 2000 mg/Kg doses). The data presented here constitute the most complete study on the genotoxic potential of X. strumarium L. and show that the extract can induce in vitro DNA damage at cytotoxic concentrations. PMID:25025061</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28193732','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28193732"><span>Error-prone meiotic division and subfertility in mice with oocyte-conditional knockdown of pericentrin.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Baumann, Claudia; Wang, Xiaotian; Yang, Luhan; Viveiros, Maria M</p>
<p>2017-04-01</p>
<p>Mouse oocytes lack canonical centrosomes and instead contain unique acentriolar microtubule-organizing centers (aMTOCs). To test the function of these distinct aMTOCs in meiotic spindle formation, pericentrin (Pcnt), an essential centrosome/MTOC protein, was knocked down exclusively in oocytes by using a transgenic RNAi approach. Here, we provide evidence that disruption of aMTOC function in oocytes promotes spindle instability and severe meiotic errors that lead to pronounced female subfertility. Pcnt-depleted oocytes from transgenic (Tg) mice were ovulated at the metaphase-II stage, but show significant chromosome misalignment, aneuploidy and premature sister chromatid separation. These defects were associated with loss of key Pcnt-interacting proteins (γ-tubulin, Nedd1 and Cep215) from meiotic spindle poles, altered spindle structure and chromosome-microtubule attachment errors. Live-cell imaging revealed disruptions in the dynamics of spindle assembly and organization, together with chromosome attachment and congression defects. Notably, spindle formation was dependent on Ran GTPase activity in Pcnt-deficient oocytes. Our findings establish that meiotic division is highly error-prone in the absence of Pcnt and disrupted aMTOCs, similar to what reportedly occurs in human oocytes. Moreover, these data underscore crucial differences between MTOC-dependent and -independent meiotic spindle assembly. © 2017. Published by The Company of Biologists Ltd.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26446309','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26446309"><span>Stacked thin layers of metaphase chromatin explain the geometry of chromosome rearrangements and banding.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Daban, Joan-Ramon</p>
<p>2015-10-08</p>
<p>The three-dimensional organization of tightly condensed chromatin within metaphase chromosomes has been one of the most challenging problems in structural biology since the discovery of the nucleosome. This study shows that chromosome images obtained from typical banded karyotypes and from different multicolour cytogenetic analyses can be used to gain information about the internal structure of chromosomes. Chromatin bands and the connection surfaces in sister chromatid exchanges and in cancer translocations are planar and orthogonal to the chromosome axis. Chromosome stretching produces band splitting and even the thinnest bands are orthogonal and well defined, indicating that short stretches of DNA can occupy completely the chromosome cross-section. These observations impose strong physical constraints on models that attempt to explain chromatin folding in chromosomes. The thin-plate model, which consists of many stacked layers of planar chromatin perpendicular to the chromosome axis, is compatible with the observed orientation of bands, with the existence of thin bands, and with band splitting; it is also compatible with the orthogonal orientation and planar geometry of the connection surfaces in chromosome rearrangements. The results obtained provide a consistent interpretation of the chromosome structural properties that are used in clinical cytogenetics for the diagnosis of hereditary diseases and cancers.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4151221','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4151221"><span>Hypomorphism in human NSMCE2 linked to primordial dwarfism and insulin resistance</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Payne, Felicity; Colnaghi, Rita; Rocha, Nuno; Seth, Asha; Harris, Julie; Carpenter, Gillian; Bottomley, William E.; Wheeler, Eleanor; Wong, Stephen; Saudek, Vladimir; Savage, David; O’Rahilly, Stephen; Carel, Jean-Claude; Barroso, Inês; O’Driscoll, Mark; Semple, Robert</p>
<p>2014-01-01</p>
<p>Structural maintenance of chromosomes (SMC) complexes are essential for maintaining chromatin structure and regulating gene expression. Two the three known SMC complexes, cohesin and condensin, are important for sister chromatid cohesion and condensation, respectively; however, the function of the third complex, SMC5–6, which includes the E3 SUMO-ligase NSMCE2 (also widely known as MMS21) is less clear. Here, we characterized 2 patients with primordial dwarfism, extreme insulin resistance, and gonadal failure and identified compound heterozygous frameshift mutations in NSMCE2. Both mutations reduced NSMCE2 expression in patient cells. Primary cells from one patient showed increased micronucleus and nucleoplasmic bridge formation, delayed recovery of DNA synthesis, and reduced formation of foci containing Bloom syndrome helicase (BLM) after hydroxyurea-induced replication fork stalling. These nuclear abnormalities in patient dermal fibroblast were restored by expression of WT NSMCE2, but not a mutant form lacking SUMO-ligase activity. Furthermore, in zebrafish, knockdown of the NSMCE2 ortholog produced dwarfism, which was ameliorated by reexpression of WT, but not SUMO-ligase–deficient NSMCE. Collectively, these findings support a role for NSMCE2 in recovery from DNA damage and raise the possibility that loss of its function produces dwarfism through reduced tolerance of replicative stress. PMID:25105364</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25105364','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25105364"><span>Hypomorphism in human NSMCE2 linked to primordial dwarfism and insulin resistance.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Payne, Felicity; Colnaghi, Rita; Rocha, Nuno; Seth, Asha; Harris, Julie; Carpenter, Gillian; Bottomley, William E; Wheeler, Eleanor; Wong, Stephen; Saudek, Vladimir; Savage, David; O'Rahilly, Stephen; Carel, Jean-Claude; Barroso, Inês; O'Driscoll, Mark; Semple, Robert</p>
<p>2014-09-01</p>
<p>Structural maintenance of chromosomes (SMC) complexes are essential for maintaining chromatin structure and regulating gene expression. Two the three known SMC complexes, cohesin and condensin, are important for sister chromatid cohesion and condensation, respectively; however, the function of the third complex, SMC5-6, which includes the E3 SUMO-ligase NSMCE2 (also widely known as MMS21) is less clear. Here, we characterized 2 patients with primordial dwarfism, extreme insulin resistance, and gonadal failure and identified compound heterozygous frameshift mutations in NSMCE2. Both mutations reduced NSMCE2 expression in patient cells. Primary cells from one patient showed increased micronucleus and nucleoplasmic bridge formation, delayed recovery of DNA synthesis, and reduced formation of foci containing Bloom syndrome helicase (BLM) after hydroxyurea-induced replication fork stalling. These nuclear abnormalities in patient dermal fibroblast were restored by expression of WT NSMCE2, but not a mutant form lacking SUMO-ligase activity. Furthermore, in zebrafish, knockdown of the NSMCE2 ortholog produced dwarfism, which was ameliorated by reexpression of WT, but not SUMO-ligase-deficient NSMCE. Collectively, these findings support a role for NSMCE2 in recovery from DNA damage and raise the possibility that loss of its function produces dwarfism through reduced tolerance of replicative stress.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2811031','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2811031"><span>Yeast cohesin complex embraces 2 micron plasmid sisters in a tri-linked catenane complex</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Ghosh, Santanu K.; Huang, Chu-Chun; Hajra, Sujata; Jayaram, Makkuni</p>
<p>2010-01-01</p>
<p>Sister chromatid cohesion, crucial for faithful segregation of replicated chromosomes in eukaryotes, is mediated by the multi-subunit protein complex cohesin. The Saccharomyces cerevisiae plasmid 2 micron circle mimics chromosomes in assembling cohesin at its partitioning locus. The plasmid is a multi-copy selfish DNA element that resides in the nucleus and propagates itself stably, presumably with assistance from cohesin. In metaphase cell lysates, or fractions enriched for their cohesed state by sedimentation, plasmid molecules are trapped topologically by the protein ring formed by cohesin. They can be released from cohesin’s embrace either by linearizing the DNA or by cleaving a cohesin subunit. Assays using two distinctly tagged cohesin molecules argue against the hand-cuff (an associated pair of monomeric cohesin rings) or the bracelet (a dimeric cohesin ring) model as responsible for establishing plasmid cohesion. Our cumulative results most easily fit a model in which a single monomeric cohesin ring, rather than a series of such rings, conjoins a pair of sister plasmids. These features of plasmid cohesion account for its sister-to-sister mode of segregation by cohesin disassembly during anaphase. The mechanistic similarities of cohesion between mini-chromosome sisters and 2 micron plasmid sisters suggest a potential kinship between the plasmid partitioning locus and centromeres. PMID:19920123</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/12221113','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/12221113"><span>Distinct chromosome segregation roles for spindle checkpoint proteins.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Warren, Cheryl D; Brady, D Michelle; Johnston, Raymond C; Hanna, Joseph S; Hardwick, Kevin G; Spencer, Forrest A</p>
<p>2002-09-01</p>
<p>The spindle checkpoint plays a central role in the fidelity of chromosome transmission by ensuring that anaphase is initiated only after kinetochore-microtubule associations of all sister chromatid pairs are complete. In this study, we find that known spindle checkpoint proteins do not contribute equally to chromosome segregation fidelity in Saccharomyces cerevisiae. Loss of Bub1 or Bub3 protein elicits the largest effect. Analysis of Bub1p reveals the presence of two molecular functions. An N-terminal 608-amino acid (nonkinase) portion of the protein supports robust checkpoint activity, and, as expected, contributes to chromosome segregation. A C-terminal kinase-encoding segment independently contributes to chromosome segregation through an unknown mechanism. Both molecular functions depend on association with Bub3p. A 156-amino acid fragment of Bub1p functions in Bub3p binding and in kinetochore localization by one-hybrid assay. An adjacent segment is required for Mad1p binding, detected by deletion analysis and coimmunoprecipitation. Finally, overexpression of wild-type BUB1 or MAD3 genes leads to chromosome instability. Analysis of this activity indicates that the Bub3p-binding domain of Bub1p contributes to this phenotype through disruption of checkpoint activity as well as through introduction of kinetochore or spindle damage.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=124140','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=124140"><span>Distinct Chromosome Segregation Roles for Spindle Checkpoint Proteins</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Warren, Cheryl D.; Brady, D. Michelle; Johnston, Raymond C.; Hanna, Joseph S.; Hardwick, Kevin G.; Spencer, Forrest A.</p>
<p>2002-01-01</p>
<p>The spindle checkpoint plays a central role in the fidelity of chromosome transmission by ensuring that anaphase is initiated only after kinetochore-microtubule associations of all sister chromatid pairs are complete. In this study, we find that known spindle checkpoint proteins do not contribute equally to chromosome segregation fidelity in Saccharomyces cerevisiae. Loss of Bub1 or Bub3 protein elicits the largest effect. Analysis of Bub1p reveals the presence of two molecular functions. An N-terminal 608-amino acid (nonkinase) portion of the protein supports robust checkpoint activity, and, as expected, contributes to chromosome segregation. A C-terminal kinase-encoding segment independently contributes to chromosome segregation through an unknown mechanism. Both molecular functions depend on association with Bub3p. A 156-amino acid fragment of Bub1p functions in Bub3p binding and in kinetochore localization by one-hybrid assay. An adjacent segment is required for Mad1p binding, detected by deletion analysis and coimmunoprecipitation. Finally, overexpression of wild-type BUB1 or MAD3 genes leads to chromosome instability. Analysis of this activity indicates that the Bub3p-binding domain of Bub1p contributes to this phenotype through disruption of checkpoint activity as well as through introduction of kinetochore or spindle damage. PMID:12221113</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22008529','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22008529"><span>Olive (Olea europaea L.) leaf extract counteracts genotoxicity and oxidative stress of permethrin in human lymphocytes.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Türkez, Hasan; Toğar, Başak</p>
<p>2011-10-01</p>
<p>The aim of this study was to investigate the protective effects of olive leaf extract (OLE) on genotoxicity and oxidative damage in cultured human blood cells treated with permethrin (PM) in the presence of a rat liver S9 mix containing cytochrome P 450 enzymes. Anti-genotoxic activities of OLE were studied using sister chromatid exchange (SCE) and chromosome aberration (CA) tests and furthermore total antioxidant capacity (TAC) and total oxidative status (TOS) were examined to determine the oxidative damage. Our results clearly revealed that treatment with PM (200 mg/l) alone increased SCE and CA rates and TOS level, decreased TAC level in cultured human blood cells. The OLE alone at the all tested doses did not induce any significant changes in the genotoxicity endpoint. However OLE leads to increases of plasma TAC level in vitro. OLE starts showing this positive effect at 100 mg/l. The combined treatment showed significant improvements in cytogenetic and biochemical parameters tested. Moreover, this improvement was more pronounced in the group received the high dose of the OLE. It could be concluded that the ethanol extract of OLE induced its genoprotective effect via the increase in the antioxidant capacity, inhibition of oxidative stress and scavenging of free radicals.</p>
</li>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28426272','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28426272"><span>Temperature-dependent regulation of rDNA condensation in Saccharomyces cerevisiae.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Shen, Donglai; Skibbens, Robert V</p>
<p>2017-06-03</p>
<p>Chromatin condensation during mitosis produces detangled and discrete DNA entities required for high fidelity sister chromatid segregation during mitosis and positions DNA away from the cleavage furrow during cytokinesis. Regional condensation during G1 also establishes a nuclear architecture through which gene transcription is regulated but remains plastic so that cells can respond to changes in nutrient levels, temperature and signaling molecules. To date, however, the potential impact of this plasticity on mitotic chromosome condensation remains unknown. Here, we report results obtained from a new condensation assay that wildtype budding yeast cells exhibit dramatic changes in rDNA conformation in response to temperature. rDNA hypercondenses in wildtype cells maintained at 37°C, compared with cells maintained at 23°C. This hypercondensation machinery can be activated during preanaphase but readily inactivated upon exposure to lower temperatures. Extended mitotic arrest at 23°C does not result in hypercondensation, negating a kinetic-based argument in which condensation that typically proceeds slowly is accelerated when cells are placed at 37°C. Neither elevated recombination nor reduced transcription appear to promote this hypercondensation. This heretofore undetected temperature-dependent hypercondensation pathway impacts current views of chromatin structure based on conditional mutant gene analyses and significantly extends our understanding of physiologic changes in chromatin architecture in response to hypothermia.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5499843','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5499843"><span>Temperature-dependent regulation of rDNA condensation in Saccharomyces cerevisiae</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Shen, Donglai; Skibbens, Robert V.</p>
<p>2017-01-01</p>
<p>ABSTRACT Chromatin condensation during mitosis produces detangled and discrete DNA entities required for high fidelity sister chromatid segregation during mitosis and positions DNA away from the cleavage furrow during cytokinesis. Regional condensation during G1 also establishes a nuclear architecture through which gene transcription is regulated but remains plastic so that cells can respond to changes in nutrient levels, temperature and signaling molecules. To date, however, the potential impact of this plasticity on mitotic chromosome condensation remains unknown. Here, we report results obtained from a new condensation assay that wildtype budding yeast cells exhibit dramatic changes in rDNA conformation in response to temperature. rDNA hypercondenses in wildtype cells maintained at 37°C, compared with cells maintained at 23°C. This hypercondensation machinery can be activated during preanaphase but readily inactivated upon exposure to lower temperatures. Extended mitotic arrest at 23°C does not result in hypercondensation, negating a kinetic-based argument in which condensation that typically proceeds slowly is accelerated when cells are placed at 37°C. Neither elevated recombination nor reduced transcription appear to promote this hypercondensation. This heretofore undetected temperature-dependent hypercondensation pathway impacts current views of chromatin structure based on conditional mutant gene analyses and significantly extends our understanding of physiologic changes in chromatin architecture in response to hypothermia. PMID:28426272</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29158426','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29158426"><span>Cohesin Function in Cohesion, Condensation, and DNA Repair Is Regulated by Wpl1p via a Common Mechanism in Saccharomyces cerevisiae.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Bloom, Michelle S; Koshland, Douglas; Guacci, Vincent</p>
<p>2018-01-01</p>
<p>Cohesin tethers DNA to mediate sister chromatid cohesion, chromosome condensation, and DNA repair. How the cell regulates cohesin to perform these distinct functions remains to be elucidated. One cohesin regulator, Wpl1p, was characterized in Saccharomyces cerevisiae as a promoter of efficient cohesion and an inhibitor of condensation. Wpl1p is also required for resistance to DNA-damaging agents. Here, we provide evidence that Wpl1p promotes the timely repair of DNA damage induced during S-phase. Previous studies have indicated that Wpl1p destabilizes cohesin's binding to DNA by modulating the interface between the cohesin subunits Mcd1p and Smc3p Our results suggest that Wpl1p likely modulates this interface to regulate all of cohesin's biological functions. Furthermore, we show that Wpl1p regulates cohesion and condensation through the formation of a functional complex with another cohesin-associated factor, Pds5p In contrast, Wpl1p regulates DNA repair independently of its interaction with Pds5p Together, these results suggest that Wpl1p regulates distinct biological functions of cohesin by Pds5p-dependent and -independent modulation of the Smc3p/Mcd1p interface. Copyright © 2018 by the Genetics Society of America.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5753852','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5753852"><span>Cohesin Function in Cohesion, Condensation, and DNA Repair Is Regulated by Wpl1p via a Common Mechanism in Saccharomyces cerevisiae</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Bloom, Michelle S.; Koshland, Douglas; Guacci, Vincent</p>
<p>2018-01-01</p>
<p>Cohesin tethers DNA to mediate sister chromatid cohesion, chromosome condensation, and DNA repair. How the cell regulates cohesin to perform these distinct functions remains to be elucidated. One cohesin regulator, Wpl1p, was characterized in Saccharomyces cerevisiae as a promoter of efficient cohesion and an inhibitor of condensation. Wpl1p is also required for resistance to DNA-damaging agents. Here, we provide evidence that Wpl1p promotes the timely repair of DNA damage induced during S-phase. Previous studies have indicated that Wpl1p destabilizes cohesin’s binding to DNA by modulating the interface between the cohesin subunits Mcd1p and Smc3p. Our results suggest that Wpl1p likely modulates this interface to regulate all of cohesin’s biological functions. Furthermore, we show that Wpl1p regulates cohesion and condensation through the formation of a functional complex with another cohesin-associated factor, Pds5p. In contrast, Wpl1p regulates DNA repair independently of its interaction with Pds5p. Together, these results suggest that Wpl1p regulates distinct biological functions of cohesin by Pds5p-dependent and -independent modulation of the Smc3p/Mcd1p interface. PMID:29158426</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25552539','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25552539"><span>Genotoxicity in primary human peripheral lymphocytes after exposure to lithium titanate nanoparticles in vitro.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Akbaba, Giray B; Turkez, Hasan; Sönmez, Erdal; Tatar, Abdulgani; Yilmaz, Mehmet</p>
<p>2016-08-01</p>
<p>Lithium titanate (Li 2 TiO 3 ) nanoparticles (LTT NPs; <100 nm) are widely used in battery technology, porcelain enamels, and ceramic insulating bodies. With the increased applications of LTT NPs, the concerns about their potential human toxicity effects and their environmental impact were also increased. However, toxicity data for LTT NPs relating to human health are very limited. Therefore, the purpose of this study was to evaluate whether LTT NPs are able to induce genetic damage in human peripheral lymphocytes in vitro when taking into consideration that DNA damage plays an important role in carcinogenesis. With this aim, the chromosome aberrations (CA), sister chromatid exchanges (SCE), and micronucleus (MN) assays were used as genotoxicity end points. Human peripheral lymphocytes obtained from five healthy male volunteers were exposed to LTT NPs at final dispersed concentrations ranging from 0 to 1000 μg/mL for 72 h at 37°C. The obtained results indicated that LTT NPs compound did not induce DNA damage in human peripheral lymphocytes as depicted by CA/cell, SCE/cell, and MN/1000 cell values in all concentrations tested. In summary, our results revealed that exposure to LTT NPs is not capable of inducing DNA lesions in human peripheral lymphocytes for the first time. © The Author(s) 2014.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28497540','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28497540"><span>Meikin-associated polo-like kinase specifies Bub1 distribution in meiosis I.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Miyazaki, Seira; Kim, Jihye; Yamagishi, Yuya; Ishiguro, Tadashi; Okada, Yuki; Tanno, Yuji; Sakuno, Takeshi; Watanabe, Yoshinori</p>
<p>2017-06-01</p>
<p>In meiosis I, sister chromatids are captured by microtubules emanating from the same pole (mono-orientation), and centromeric cohesion is protected throughout anaphase. Shugoshin, which is localized to centromeres depending on the phosphorylation of histone H2A by Bub1 kinase, plays a central role in protecting meiotic cohesin Rec8 from separase cleavage. Another key meiotic kinetochore factor, meikin, may regulate cohesion protection, although the underlying molecular mechanisms remain elusive. Here, we show that fission yeast Moa1 (meikin), which associates stably with CENP-C during meiosis I, recruits Plo1 (polo-like kinase) to the kinetochores and phosphorylates Spc7 (KNL1) to accumulate Bub1. Consequently, in contrast to the transient kinetochore localization of mitotic Bub1, meiotic Bub1 persists at kinetochores until anaphase I. The meiotic Bub1 pool ensures robust Sgo1 (shugoshin) localization and cohesion protection at centromeres by cooperating with heterochromatin protein Swi6, which binds and stabilizes Sgo1. Furthermore, molecular genetic analyses show a hierarchical regulation of centromeric cohesion protection by meikin and shugoshin that is important for establishing meiosis-specific chromosome segregation. We provide evidence that the meiosis-specific Bub1 regulation is conserved in mouse. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25231917','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25231917"><span>Genotoxic evaluation of terbinafine in human lymphocytes in vitro.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Tolomeotti, Danielle; de Castro-Prado, Marialba Avezum Alves; de Sant'Anna, Juliane Rocha; Martins, Ana Beatriz Tozzo; Della-Rosa, Valter Augusto</p>
<p>2015-01-01</p>
<p>Terbinafine is an antimycotic drug usually used against several superficial fungal infections and with a potential application in the treatment of human cancers. Since to date there are few data on the genotoxic effects of terbinafine in mammalian cells, current study evaluated the potential genotoxic of such antifungal agent in cultured human peripheral blood lymphocytes. Terbinafine was used at the peak plasma concentration (1.0 μg/ml) and in four additional concentrations higher than the human plasmatic peak (5.0 μg/ml, 25.0 μg/ml, 50.0 μg/ml and 100.0 μg/ml). Chromosomal aberrations (CA), sister chromatid exchanges (SCE), micronuclei (MN), nucleoplasmic bridges (NP) and nuclear buds (NB) were scored as genetic endpoints. In all analysis no significant differences (α = 0.05, Kruskal-Wallis test) were observed. Complementary criterion adopted to obtain the final response in cytogenetic agreed with statistical results. Therefore, results of this study showed that terbinafine neither induced CA, SCE, MN, NP and NB nor affected significantly mitotic, replication and cytokinesis-block proliferation indices in any of the tested concentrations. It may be assumed that terbinafine was not genotoxic or cytotoxic to cultured human peripheral blood lymphocytes in our experimental conditions.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3418308','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3418308"><span>Pac-man motility of kinetochores unleashed by laser microsurgery</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>LaFountain, James R.; Cohan, Christopher S.; Oldenbourg, Rudolf</p>
<p>2012-01-01</p>
<p>We report on experiments directly in living cells that reveal the regulation of kinetochore function by tension. X and Y sex chromosomes in crane fly (Nephrotoma suturalis) spermatocytes exhibit an atypical segregation mechanism in which each univalent maintains K-fibers to both poles. During anaphase, each maintains a leading fiber (which shortens) to one pole and a trailing fiber (which elongates) to the other. We used this intriguing behavior to study the motile states that X-Y kinetochores are able to support during anaphase. We used a laser microbeam to either sever a univalent along the plane of sister chromatid cohesion or knock out one of a univalent's two kinetochores to release one or both from the resistive influence of its sister's K-fiber. Released kinetochores with attached chromosome arms moved poleward at rates at least two times faster than normal. Furthermore, fluorescent speckle microscopy revealed that detached kinetochores converted their functional state from reverse pac-man to pac-man motility as a consequence of their release from mechanical tension. We conclude that kinetochores can exhibit pac-man motility, even though their normal behavior is dominated by traction fiber mechanics. Unleashing of kinetochore motility through loss of resistive force is further evidence for the emerging model that kinetochores are subject to tension-sensitive regulation. PMID:22740625</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21538557','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21538557"><span>Analysis of genomic instability in the offspring of fathers exposed to low doses of ionizing radiation.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Aghajanyan, Anna; Kuzmina, Nina; Sipyagyna, Alla; Baleva, Larisa; Suskov, Igor</p>
<p>2011-08-01</p>
<p>Transgenerational genomic instability was studied in nonirradiated children born from fathers who were irradiated with low doses of ionizing radiation while working as clean-up workers at the Chernobyl Nuclear Power Plant (liquidators) and nonirradiated mothers from nuclear families. Aberrant cell frequencies (ACFs), chromosomal type aberration frequencies, and chromatid break frequencies (CBFs) in the lymphocytes of fathers-liquidators, and their children were significantly higher when compared with the control group (P < 0.05). Individual ACFs, aberration frequencies, and CBFs were independent of the time between irradiation of the father and conception of the child (1 month to 18 years). Chromosomes were categorized into seven groups (A through G). Analysis of aberrant chromosomes within these groups showed no differences in the average frequency of aberrant chromosomes between children and fathers-liquidators. However, significant differences were observed in the average frequency of aberrant chromosomes in groups A, B, and C between children and mothers in the families of liquidators. These results suggest that low doses of radiation induce genomic instability in fathers. Moreover, low radiation doses might be responsible for individual peculiarities in transgenerational genomic instability in children (as a consequence of response to primary DNA damage). Thus, genomic instability may contribute to increased morbidity over the lifetime of these children. Copyright © 2011 Wiley-Liss, Inc.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28383696','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28383696"><span>The LSH/HELLS homolog Irc5 contributes to cohesin association with chromatin in yeast.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Litwin, Ireneusz; Bakowski, Tomasz; Maciaszczyk-Dziubinska, Ewa; Wysocki, Robert</p>
<p>2017-06-20</p>
<p>Accurate chromosome segregation is essential for every living cell as unequal distribution of chromosomes during cell division may result in genome instability that manifests in carcinogenesis and developmental disorders. Irc5 from Saccharomyces cerevisiae is a member of the conserved Snf2 family of ATP-dependent DNA translocases and its function is poorly understood. Here, we identify Irc5 as a novel interactor of the cohesin complex. Irc5 associates with Scc1 cohesin subunit and contributes to cohesin binding to chromatin. Disruption of IRC5 decreases cohesin levels at centromeres and chromosome arms, causing premature sister chromatid separation. Moreover, reduced cohesin occupancy at the rDNA region in cells lacking IRC5 leads to the loss of rDNA repeats. We also show that the translocase activity of Irc5 is required for its function in cohesion pathway. Finally, we demonstrate that in the absence of Irc5 both the level of chromatin-bound Scc2, a member of cohesin loading complex, and physical interaction between Scc1 and Scc2 are reduced. Our results suggest that Irc5 is an auxiliary factor that is involved in cohesin association with chromatin. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4612677','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4612677"><span>Inactivation of the budding yeast cohesin loader Scc2 alters gene expression both globally and in response to a single DNA double strand break</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Lindgren, Emma; Hägg, Sara; Giordano, Fosco; Björkegren, Johan; Ström, Lena</p>
<p>2014-01-01</p>
<p>Genome integrity is fundamental for cell survival and cell cycle progression. Important mechanisms for keeping the genome intact are proper sister chromatid segregation, correct gene regulation and efficient repair of damaged DNA. Cohesin and its DNA loader, the Scc2/4 complex have been implicated in all these cellular actions. The gene regulation role has been described in several organisms. In yeast it has been suggested that the proteins in the cohesin network would effect transcription based on its role as insulator. More recently, data are emerging indicating direct roles for gene regulation also in yeast. Here we extend these studies by investigating whether the cohesin loader Scc2 is involved in regulation of gene expression. We performed global gene expression profiling in the absence and presence of DNA damage, in wild type and Scc2 deficient G2/M arrested cells, when it is known that Scc2 is important for DNA double strand break repair and formation of damage induced cohesion. We found that not only the DNA damage specific transcriptional response is distorted after inactivation of Scc2 but also the overall transcription profile. Interestingly, these alterations did not correlate with changes in cohesin binding. PMID:25483075</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26929995','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26929995"><span>Genotoxicity of monosodium glutamate.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Ataseven, Nazmiye; Yüzbaşıoğlu, Deniz; Keskin, Ayten Çelebi; Ünal, Fatma</p>
<p>2016-05-01</p>
<p>Monosodium glutamate (MSG) is one of the most widely used flavor enhancers throughout the world. The aim of this study is to investigate the genotoxic potential of MSG by using chromosome aberrations (CAs), sister-chromatid exchanges (SCEs), cytokinesis-blocked micronucleus (CBMN), and random amplified polymorphic DNA-polimerase chain reaction (RAPD-PCR) in cultured human lymphocytes and alkaline comet assays in isolated human lymphocytes, which were incubated with six concentrations (250, 500, 1000, 2000, 4000 and 8000 μg/mL) of MSG. The result of this study indicated that MSG significantly and dose dependently increased the frequencies of CAs, SCE and MN in all treatments and times, compared with control. However, the replication (RI) and nuclear division indices (NDI) were not affected. In this paper, in vitro genotoxic effects of the MSG was also investigated on human peripheral lymphocytes by analysing the RAPD-PCR with arbitrary 10-mer primers. The changes occurring in RAPD profiles after MSG treatment include increase or decrease in band intensity and gain or loss of bands. In the comet assay, this additive caused DNA damage at all concentrations in isolated human lymphocytes after 1-h in vitro exposure. Our results demonstrate that MSG is genotoxic to the human peripheral blood lymphocytes in vitro. Copyright © 2016. Published by Elsevier Ltd.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/14615892','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/14615892"><span>Replication labeling patterns and chromosome territories typical of mammalian nuclei are conserved in the early metazoan Hydra.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Alexandrova, Olga; Solovei, Irina; Cremer, Thomas; David, Charles N</p>
<p>2003-12-01</p>
<p>To investigate the evolutionary conservation of higher order nuclear architecture previously described for mammalian cells we have analyzed the nuclear architecture of the simple polyp Hydra. These diploblastic organisms have large nuclei (8-10 microm) containing about 3x10(9) bp of DNA organized in 15 chromosome pairs. They belong to the earliest metazoan phylum and are separated from mammals by at least 600 million years. Single and double pulse labeling with halogenated nucleotides (bromodeoxyuridine, iododeoxyuridine and chlorodeoxyuridine) revealed striking similarities to the known sequence of replication labeling patterns in mammalian nuclei. These patterns reflect a persistent nuclear arrangement of early, mid-, and late replicating chromatin foci that could be identified during all stages of interphase over at least 5-10 cell generations. Segregation of labeled chromatids led after several cell divisions to nuclei with single or a few labeled chromosome territories. In such nuclei distinct clusters of labeled chromatin foci were separated by extended nuclear areas with non-labeled chromatin, which is typical of a territorial arrangement of interphase chromosomes. Our results indicate the conservation of fundamental features of higher order chromatin arrangements throughout the evolution of metazoan animals and suggest the existence of conserved mechanism(s) controlling this architecture.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19968867','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19968867"><span>Chromosome r(10)(p15.3q26.12) in a newborn child: case report.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Gunnarsson, Cecilia; Graffmann, Barbara; Jonasson, Jon</p>
<p>2009-12-07</p>
<p>Ring chromosome 10 is a rare cytogenetic finding. Of the less than 10 reported cases we have found in the literature, none was characterized using high-resolution microarray analysis. Ring chromosomes are frequently unstable due to sister chromatid exchanges and mitotic failures. When mosaicism is present, the interpretation of genotype-phenotype correlations becomes extremely difficult. We report on a newborn girl with growth retardation, microcephaly, congenital heart defects, dysmorphic features and psychomotor retardation. Karyotyping revealed a non-mosaic apparently stable ring chromosome 10 replacing one of the normal homologues in all analyzed metaphases. High-resolution oligonucleotide microarray analysis showed a de novo approximately 12.5 Mb terminal deletion 10q26.12 -> qter and a corresponding 285 kb terminal deletion of 10pter -> p15.3. This case demonstrates that an increased nuchal translucency thickness detected by early ultrasonography should preferably lead to not only QF-PCR for the diagnosis of Down syndrome but also karyotyping. In the future, microarray analysis, which needs further evaluation, might become the method of choice. The clinical phenotype of our patient was in agreement with that of patients with a terminal 10q deletion. For the purpose of genotype-phenotype analysis, there seems to be no need for a "ring syndrome" concept.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21511894','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21511894"><span>Anti-oxidative and anti-genotoxic effects of methanolic extract of Mentha pulegium on human lymphocyte culture.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Alpsoy, Lokman; Sahin, Hilal; Karaman, Seyda</p>
<p>2011-08-01</p>
<p>In the present work, methanolic extract of Mentha pulegium from Erzurum, Turkey, was used in order to report the results of anti-oxidant capacity, anti-oxidant activity and anti-genotoxic effects. The total antioxidant capacity and total phenolic content were measured by using CUPRAC, ABTS and Folin-Ciocalteu colorimetric methods. The total phenolic content was higher than the total antioxidant capacity (for the results of both the CUPRAC and ABTS methods) of methanolic extract of M pulegium (ME). Also, we evaluated the anti-oxidant enzyme activity such as superoxide dismutase (SOD) and glutation peroxidase, total glutation (GSH) and malondialdehyde (MDA) in human lymphocyte culture. In CCl₄-treated group, the activity of SOD, glutathione peroxidase (GPx) and GSH decreased significantly and the level of MDA increased significantly. A significant increase in the activity of SOD, GPx and the level of GSH were seen when supplemented with ME to CCl₄-treated group. Furthermore, a significant decrease in the level of MDA was observed when compared with CCl₄ alone treated group. In addition, anti-genotoxic effect of ME was studied by using sister chromatid exchange (SCE) method. As a result, ME has shown anti-genotoxic effect depend on anti-oxidative effect on human lymphocyte culture.</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1461899','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1461899"><span>Inherited differences in crossing over and gene conversion frequencies between wild strains of Sordaria fimicola from "Evolution Canyon".</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Saleem, M; Lamb, B C; Nevo, E</p>
<p>2001-01-01</p>
<p>Recombination generates new combinations of existing genetic variation and therefore may be important in adaptation and evolution. We investigated whether there was natural genetic variation for recombination frequencies and whether any such variation was environment related and possibly adaptive. Crossing over and gene conversion frequencies often differed significantly in a consistent direction between wild strains of the fungus Sordaria fimicola isolated from a harsher or a milder microscale environment in "Evolution Canyon," Israel. First- and second-generation descendants from selfing the original strains from the harsher, more variable, south-facing slope had higher frequencies of crossing over in locus-centromere intervals and of gene conversion than those from the lusher north-facing slopes. There were some significant differences between strains within slopes, but these were less marked than between slopes. Such inherited variation could provide a basis for natural selection for optimum recombination frequencies in each environment. There were no significant differences in meiotic hybrid DNA correction frequencies between strains from the different slopes. The conversion analysis was made using only conversions to wild type, because estimations of conversion to mutant were affected by a high frequency of spontaneous mutation. There was no polarized segregation of chromosomes at meiosis I or of chromatids at meiosis II. PMID:11779798</p>
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<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11779798','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11779798"><span>Inherited differences in crossing over and gene conversion frequencies between wild strains of Sordaria fimicola from "Evolution Canyon".</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Saleem, M; Lamb, B C; Nevo, E</p>
<p>2001-12-01</p>
<p>Recombination generates new combinations of existing genetic variation and therefore may be important in adaptation and evolution. We investigated whether there was natural genetic variation for recombination frequencies and whether any such variation was environment related and possibly adaptive. Crossing over and gene conversion frequencies often differed significantly in a consistent direction between wild strains of the fungus Sordaria fimicola isolated from a harsher or a milder microscale environment in "Evolution Canyon," Israel. First- and second-generation descendants from selfing the original strains from the harsher, more variable, south-facing slope had higher frequencies of crossing over in locus-centromere intervals and of gene conversion than those from the lusher north-facing slopes. There were some significant differences between strains within slopes, but these were less marked than between slopes. Such inherited variation could provide a basis for natural selection for optimum recombination frequencies in each environment. There were no significant differences in meiotic hybrid DNA correction frequencies between strains from the different slopes. The conversion analysis was made using only conversions to wild type, because estimations of conversion to mutant were affected by a high frequency of spontaneous mutation. There was no polarized segregation of chromosomes at meiosis I or of chromatids at meiosis II.</p>
</li>
<li>
<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26877138','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26877138"><span>Sordaria, a model system to uncover links between meiotic pairing and recombination.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Zickler, Denise; Espagne, Eric</p>
<p>2016-06-01</p>
<p>The mycelial fungus Sordaria macrospora was first used as experimental system for meiotic recombination. This review shows that it provides also a powerful cytological system for dissecting chromosome dynamics in wild-type and mutant meioses. Fundamental cytogenetic findings include: (1) the identification of presynaptic alignment as a key step in pairing of homologous chromosomes. (2) The discovery that biochemical complexes that mediate recombination at the DNA level concomitantly mediate pairing of homologs. (3) This pairing process involves not only resolution but also avoidance of chromosomal entanglements and the resolution system includes dissolution of constraining DNA recombination interactions, achieved by a unique role of Mlh1. (4) Discovery that the central components of the synaptonemal complex directly mediate the re-localization of the recombination proteins from on-axis to in-between homologue axis positions. (5) Identification of putative STUbL protein Hei10 as a structure-based signal transduction molecule that coordinates progression and differentiation of recombinational interactions at multiple stages. (6) Discovery that a single interference process mediates both nucleation of the SC and designation of crossover sites, thereby ensuring even spacing of both features. (7) Discovery of local modulation of sister-chromatid cohesion at sites of crossover recombination. Copyright © 2016 Elsevier Ltd. All rights reserved.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22987027','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22987027"><span>Molecular characterisation of murine acute myeloid leukaemia induced by 56Fe ion and 137Cs gamma ray irradiation.</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p>
<p>Steffen, Leta S; Bacher, Jeffery W; Peng, Yuanlin; Le, Phuong N; Ding, Liang-Hao; Genik, Paula C; Ray, F Andrew; Bedford, Joel S; Fallgren, Christina M; Bailey, Susan M; Ullrich, Robert L; Weil, Michael M; Story, Michael D</p>
<p>2013-01-01</p>
<p>Exposure to sparsely ionising gamma- or X-ray irradiation is known to increase the risk of leukaemia in humans. However, heavy ion radiotherapy and extended space exploration will expose humans to densely ionising high linear energy transfer (LET) radiation for which there is currently no understanding of leukaemia risk. Murine models have implicated chromosomal deletion that includes the hematopoietic transcription factor gene, PU.1 (Sfpi1), and point mutation of the second PU.1 allele as the primary cause of low-LET radiation-induced murine acute myeloid leukaemia (rAML). Using array comparative genomic hybridisation, fluorescence in situ hybridisation and high resolution melt analysis, we have confirmed that biallelic PU.1 mutations are common in low-LET rAML, occurring in 88% of samples. Biallelic PU.1 mutations were also detected in the majority of high-LET rAML samples. Microsatellite instability was identified in 42% of all rAML samples, and 89% of samples carried increased microsatellite mutant frequencies at the single-cell level, indicative of ongoing instability. Instability was also observed cytogenetically as a 2-fold increase in chromatid-type aberrations. These data highlight the similarities in molecular characteristics of high-LET and low-LET rAML and confirm the presence of ongoing chromosomal and microsatellite instability in murine rAML.</p>
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<p><a target="_blank" rel="noopener noreferrer" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2847229','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2847229"><span>Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks</span></a></p>
<p><a target="_blank" rel="noopener noreferrer" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p>
<p>Bolderson, Emma; Tomimatsu, Nozomi; Richard, Derek J.; Boucher, Didier; Kumar, Rakesh; Pandita, Tej K.; Burma, Sandeep; Khanna, Kum Kum</p>
<p>2010-01-01</p>
<p>DNA double-strand break (DSB) repair via the homologous recombination pathway is a multi-stage process, which results in repair of the DSB without loss of genetic information or fidelity. One essential step in this process is the generation of extended single-stranded DNA (ssDNA) regions at the break site. This ssDNA serves to induce cell cycle checkpoints and is required for Rad51 mediated strand invasion of the sister chromatid. Here, we show that human Exonuclease 1 (Exo1) is required for the normal repair of DSBs by HR. Cells depleted of Exo1 show chromosomal instability and hypersensitivity to ionising radiation (IR) exposure. We find that Exo1 accumulates rapidly at DSBs and is required for the recruitment of RPA and Rad51 to sites of DSBs, suggesting a role for Exo1 in ssDNA generation. Interestingly, the phosphorylation of Exo1 by ATM appears to regulate the activity of Exo1 following resection, allowing optimal Rad51 loading and the completion of HR repair. These data establish a role for Exo1 in resection of DSBs in human cells, highlighting the critical requirement of Exo1 for DSB repair via HR and thus the maintenance of genomic stability. PMID:20019063</p>
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