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Mol._Cell._Biol.-2009-Outwin-4363-75.pdf (1.98 MB)

Smc5-Smc6-dependent removal of cohesin from mitotic chromosomes

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posted on 2023-06-08, 13:32 authored by Emily OutwinEmily Outwin, Anja Irmisch, Jo Murray, Matthew J O'Connell
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

History

Publication status

  • Published

File Version

  • Published version

Journal

Molecular and Cellular Biology

ISSN

0270-7306

Publisher

American Society for Microbiology

Issue

16

Volume

29

Page range

4363-4375

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2012-11-13

First Open Access (FOA) Date

2016-03-22

First Compliant Deposit (FCD) Date

2016-11-10

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