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• W2000821622 abstract "The classical X shape of mitotic human chromosomes is the consequence of two distinct waves of cohesin removal. First, during prophase and prometaphase, the bulk of cohesin is driven from chromosome arms by the cohesin antagonist WAPL. This arm-specific cohesin removal is referred to as the prophase pathway [1Losada A. Hirano M. Hirano T. Identification of Xenopus SMC protein complexes required for sister chromatid cohesion.Genes Dev. 1998; 12: 1986-1997Crossref PubMed Scopus (517) Google Scholar, 2Waizenegger I.C. Hauf S. Meinke A. Peters J.-M. Two distinct pathways remove mammalian cohesin from chromosome arms in prophase and from centromeres in anaphase.Cell. 2000; 103: 399-410Abstract Full Text Full Text PDF PubMed Scopus (574) Google Scholar, 3Kueng S. Hegemann B. Peters B.H. Lipp J.J. Schleiffer A. Mechtler K. Peters J.-M. Wapl controls the dynamic association of cohesin with chromatin.Cell. 2006; 127: 955-967Abstract Full Text Full Text PDF PubMed Scopus (422) Google Scholar, 4Gandhi R. Gillespie P.J. Hirano T. Human Wapl is a cohesin-binding protein that promotes sister-chromatid resolution in mitotic prophase.Curr. Biol. 2006; 16: 2406-2417Abstract Full Text Full Text PDF PubMed Scopus (315) Google Scholar]. The subsequent cleavage of the remaining centromeric cohesin by Separase is known to be the trigger for anaphase onset [5Uhlmann F. Lottspeich F. Nasmyth K. Sister-chromatid separation at anaphase onset is promoted by cleavage of the cohesin subunit Scc1.Nature. 1999; 400: 37-42Crossref PubMed Scopus (753) Google Scholar, 6Uhlmann F. Wernic D. Poupart M.A. Koonin E.V. Nasmyth K. Cleavage of cohesin by the CD clan protease separin triggers anaphase in yeast.Cell. 2000; 103: 375-386Abstract Full Text Full Text PDF PubMed Scopus (651) Google Scholar, 7Oliveira R.A. Hamilton R.S. Pauli A. Davis I. Nasmyth K. Cohesin cleavage and Cdk inhibition trigger formation of daughter nuclei.Nat. Cell Biol. 2010; 12: 185-192Crossref PubMed Scopus (127) Google Scholar]. Remarkably the biological purpose of the prophase pathway is unknown. We find that this pathway is essential for two key mitotic processes. First, it is important to focus Aurora B at centromeres to allow efficient correction of erroneous microtubule-kinetochore attachments. In addition, it is required to facilitate the timely decatenation of sister chromatids. As a consequence, WAPL-depleted cells undergo anaphase with segregation errors, including both lagging chromosomes and catenanes, resulting in micronuclei and DNA damage. Stable WAPL depletion arrests cells in a p53-dependent manner but causes p53-deficient cells to become highly aneuploid. Our data show that the WAPL-dependent prophase pathway is essential for proper chromosome segregation and is crucial to maintain genomic integrity." @default.
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• W2000821622 date "2013-10-01" @default.
• W2000821622 modified "2023-10-18" @default.
• W2000821622 title "WAPL-Mediated Removal of Cohesin Protects against Segregation Errors and Aneuploidy" @default.
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• W2000821622 doi "https://doi.org/10.1016/j.cub.2013.09.003" @default.
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