PMID: identifiant
de la référence Pubmed : |
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 (22563370)  |
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| titre : |
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Bloom's Syndrome and PICH Helicases Cooperate with Topoisomerase IIα in Centromere Disjunction before Anaphase. |
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| auteur(s) : |
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Sébastien Rouzeau1, Fabrice Cordelières1, 2, Géraldine Buhagiar-Labarchède1, Ilse Hurbain2, 3, Rosine Onclercq-Delic1, Simon Gemble1, Laura Magnaghi-Jaulin4, Christian Jaulin4, Mounira Amor-Guéret ( ) 1 |
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| laboratoire : |
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| Équipe de recherche : |
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Epigénétique et cancer |
| résumé : |
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Centromeres are specialized chromosome domains that control chromosome segregation during mitosis, but little is known about the mechanisms underlying the maintenance of their integrity. Centromeric ultrafine anaphase bridges are physiological DNA structures thought to contain unresolved DNA catenations between the centromeres separating during anaphase. BLM and PICH helicases colocalize at these ultrafine anaphase bridges and promote their resolution. As PICH is detectable at centromeres from prometaphase onwards, we hypothesized that BLM might also be located at centromeres and that the two proteins might cooperate to resolve DNA catenations before the onset of anaphase. Using immunofluorescence analyses, we demonstrated the recruitment of BLM to centromeres from G2 phase to mitosis. With a combination of fluorescence in situ hybridization, electron microscopy, RNA interference, chromosome spreads and chromatin immunoprecipitation, we showed that both BLM-deficient and PICH-deficient prometaphase cells displayed changes in centromere structure. These cells also had a higher frequency of centromeric non disjunction in the absence of cohesin, suggesting the persistence of catenations. Both proteins were required for the correct recruitment to the centromere of active topoisomerase IIα, an enzyme specialized in the catenation/decatenation process. These observations reveal the existence of a functional relationship between BLM, PICH and topoisomerase IIα in the centromere decatenation process. They indicate that the higher frequency of centromeric ultrafine anaphase bridges in BLM-deficient cells and in cells treated with topoisomerase IIα inhibitors is probably due not only to unresolved physiological ultrafine anaphase bridges, but also to newly formed ultrafine anaphase bridges. We suggest that BLM and PICH cooperate in rendering centromeric catenates accessible to topoisomerase IIα, thereby facilitating correct centromere disjunction and preventing the formation of supernumerary centromeric ultrafine anaphase bridges. |
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| domaine : |
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Sciences du Vivant/Biologie cellulaire
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langue du texte
intégral : |
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Anglais |
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| ISSN : |
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1932-6203 |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1371/journal.pone.0033905 |
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| journal : |
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| PLoS ONE |
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Public Library of Science |
| ISSN |
1932-6203 |
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| Audience : |
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internationale |
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| date de publication : |
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2012 |
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date de publication
électronique : |
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26/04/2012 |
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| volume : |
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7 |
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| numéro : |
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4 |
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| page, identifiant, ... : |
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e33905 |
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| contrat, financement : |
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This work was supported by grants from the Institut Curie (PIC), the Centre National de la Recherche Scientifique (CNRS), the Cance'ropoˆ le/Re'gion Ilede- France, the Ligue contre le Cancer Grand-Ouest, the Association pour la Recherche sur le Cancer (1071), the Agence Nationale de la Recherche (EpiCentr) and by fellowships from the Ministe're de' le'gue' de l'Enseignement Supe' rieur et de la Recherche and from the Ligue Nationale contre le Cancer. |
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| Projet ANR : |
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| Référence du projet |
EpiCentr |
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