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Disruption of stem cell genomic integrity can lead to developmental abnormalities and cancer. Roles of the Smc5\/6 structural maintenance of chromosomes complex in pluripotent stem cell genome maintenance have not been investigated, despite its important roles in DNA synthesis, DNA repair and chromosome segregation as evaluated in other model systems. Using mouse embryonic stem cells (mESCs) with a conditional knockout allele of Smc5, we showed that Smc5 protein depletion resulted in destabilization of the Smc5\/6 complex, accumulation of cells in G2 phase of the cell cycle and apoptosis. Detailed assessment of mitotic mESCs revealed abnormal condensin distribution and perturbed chromosome segregation, accompanied by irregular spindle morphology, lagging chromosomes and DNA bridges. Mutation of Smc5 resulted in retention of Aurora B kinase and enrichment of condensin on chromosome arms. Furthermore, we observed reduced levels of Polo-like kinase 1 at kinetochores during mitosis. Our study reveals crucial requirements of the Smc5\/6 complex during cell cycle progression and for stem cell genome maintenance.<\/jats:p>","DOI":"10.1242\/jcs.179036","type":"journal-article","created":{"date-parts":[[2016,2,27]],"date-time":"2016-02-27T02:40:04Z","timestamp":1456540804000},"page":"1619-1634","source":"Crossref","is-referenced-by-count":24,"title":["Conditional mutation of <i>Smc5<\/i> in mouse embryonic stem cells perturbs condensin localization and mitotic progression"],"prefix":"10.1242","volume":"129","author":[{"given":"Marina V.","family":"Pryzhkova","sequence":"first","affiliation":[{"name":"Johns Hopkins University Bloomberg School of Public Health Department of Biochemistry and Molecular Biology , , Baltimore, MD 21205 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4890-2647","authenticated-orcid":false,"given":"Philip W.","family":"Jordan","sequence":"additional","affiliation":[{"name":"Johns Hopkins University Bloomberg School of Public Health Department of Biochemistry and Molecular Biology , , Baltimore, MD 21205 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","reference":[{"key":"2024061316074468100_JCS179036C1","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1101\/gad.2016411","article-title":"The initial phase of chromosome condensation requires Cdk1-mediated phosphorylation of the CAP-D3 subunit of condensin II","volume":"25","author":"Abe","year":"2011","journal-title":"Genes Dev."},{"key":"2024061316074468100_JCS179036C3","volume-title":"Manipulating the Mouse Embryo","author":"Behringer","year":"2014"},{"key":"2024061316074468100_JCS179036C4","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1083\/jcb.200912129","article-title":"Cohesinopathies, gene expression, and chromatin organization","volume":"189","author":"Bose","year":"2010","journal-title":"J. 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