For successful eukaryotic mitosis, sister chromatid pairs remain linked after replication until their kinetochores have been attached to opposite spindle poles by microtubules. This linkage is broken at the metaphase–anaphase transition and the sisters separate. In budding yeast, this sister chromatid cohesion requires a multi-protein complex called cohesin. A key component of cohesin is Scc1/Mcd1 (Rad21 in fission yeast). Disruption of the chicken orthologue of Scc1 by gene targeting in DT40 cells causes premature sister chromatid separation. Cohesion between sister chromatids is likely to provide a substrate for post-replicative DNA repair by homologous recombination. In keeping with this role of cohesion, Scc1 mutants also show defects in the repair of spontaneous and induced DNA damage. Scc1-deficient cells frequently fail to complete metaphase chromosome alignment and show chromosome segregation defects, suggesting aberrant kinetochore function. Consistent with this, the chromosomal passenger protein, INCENP (inner centromere protein) fails to localize to centromeres. Survivin, another passenger protein and one which interacts with INCENP, also fails to localize to centromeres in Scc1-deficient cells. These results show that cohesin maintains genomic stability by ensuring appropriate DNA repair and equal chromosome segregation at mitosis.
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Conference Article| February 01 2003
Sister chromatid cohesion and genome stability in vertebrate cells
C. Morrison 1
*Wellcome Centre for Cell Biology, Institute of Cell and Molecular Biology, King's Buildings, University of Edinburgh, Edinburgh, U.K.
1To whom correspondence should be addressed. Present address: Department of Biochemistry, National University of Ireland Galway, University Road, Galway, Ireland (e-mail firstname.lastname@example.org).
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Publisher: Portland Press Ltd
Online ISSN: 1470-8752
Print ISSN: 0300-5127
Copyright 2003 Biochemical Society
Biochem Soc Trans (2003) 31 (1): 263–265.
C. Morrison, P. Vagnarelli, E. Sonoda, S. Takeda, W.C. Earnshaw; Sister chromatid cohesion and genome stability in vertebrate cells. Biochem Soc Trans 1 February 2003; 31 (1): 263–265. doi: https://doi.org/10.1042/bst0310263
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