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• W1720596306 abstract "A bipolar mitotic spindle facilitates the equal segregation of chromosomes to two daughter cells. To achieve bipolar attachment of microtubules to kinetochores of sister chromatids, chromatids must remain paired after replication. This cohesion is mediated by the conserved cohesin complex comprised of SMC1, SMC3, SCC1, and either SA1 or SA2 in humans. Because defects in spindle assembly or sister chromatid cohesion can lead to aneuploidy in daughter cells, proper regulation of these processes is essential for fidelity in chromosome segregation [1Solomon D.A. Kim T. Diaz-Martinez L.A. Fair J. Elkahloun A.G. Harris B.T. Toretsky J.A. Rosenberg S.A. Shukla N. Ladanyi M. et al.Mutational inactivation of STAG2 causes aneuploidy in human cancer.Science. 2011; 333: 1039-1043Crossref PubMed Scopus (331) Google Scholar]. In an RNAi screen for regulators of spindle assembly, we identify the deubiquitinase USP37 as a regulator of mitotic progression, centrosome integrity, and chromosome alignment. USP37 associates with cohesin and contributes to sister chromatid resolution. Cohesion defects are rescued by expression of an RNAi-resistant USP37, but not the catalytically impaired USP37C350A mutant. Further, USP37 associates with WAPL, a negative regulator of cohesion necessary for cohesin release in prophase [2Gandhi 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, 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 (421) Google Scholar], in a manner dependent on USP37’s second and third ubiquitin-interacting motifs. Depletion of USP37 reduces the stability of chromatin-associated WAPL and increases the fraction of WAPL that is more heavily ubiquitylated in mitosis. Consistently, overexpression of USP37C350A results in increased modification of WAPL, and addition of purified USP37WT, but not USP37C350A, to WAPL immunoprecipitates results in a reduction of ubiquitylated products. Taken together, our results ascribe a novel function for USP37 in mitotic progression and further suggest that USP37 positively regulates the stability of chromatin-associated WAPL to facilitate sister chromatid resolution." @default.
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• W1720596306 date "2015-08-01" @default.
• W1720596306 modified "2023-09-23" @default.
• W1720596306 title "The Deubiquitinase USP37 Regulates Chromosome Cohesion and Mitotic Progression" @default.
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• W1720596306 doi "https://doi.org/10.1016/j.cub.2015.07.025" @default.
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