Smc5-Smc6-dependent removal of cohesin from mitotic chromosomes

Outwin, Emily A, Irmisch, Anja, Murray, Johanne M and O'Connell, Matthew J (2009) Smc5-Smc6-dependent removal of cohesin from mitotic chromosomes. Molecular and Cellular Biology, 29 (16). pp. 4363-4375. ISSN 0270-7306

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Abstract

The function of the essential cohesin-related Smc5-Smc6 complex has remained elusive, though hypomorphic mutants have defects late in recombination, in checkpoint maintenance, and in chromosome segregation. Recombination and checkpoints are not essential for viability, and Smc5-Smc6-null mutants die in lethal mitoses. This suggests that the chromosome segregation defects may be the source of lethality in irradiated Smc5-Smc6 hypomorphs. We show that in smc6 mutants, following DNA damage in interphase, chromosome arm segregation fails due to an aberrant persistence of cohesin, which is normally removed by the Separase-independent pathway. This postanaphase persistence of cohesin is not dependent on DNA damage, since the synthetic lethality of smc6 hypomorphs with a topoisomerase II mutant, defective in mitotic chromosome structure, is also due to the retention of cohesin on undamaged chromosome arms. In both cases, Separase overexpression bypasses the defect and restores cell viability, showing that defective cohesin removal is a major determinant of the mitotic lethality of Smc5-Smc6 mutants

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science > Q Science (General)
Q Science > QR Microbiology > QR0001 General
Depositing User: Johanne Murray
Date Deposited: 13 Nov 2012 14:24
Last Modified: 06 Mar 2017 19:44
URI: http://sro.sussex.ac.uk/id/eprint/42145

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