Format

Send to:

Choose Destination
See comment in PubMed Commons below
Mol Cell Biol. 2009 Aug;29(16):4363-75. doi: 10.1128/MCB.00377-09. Epub 2009 Jun 15.

Smc5-Smc6-dependent removal of cohesin from mitotic chromosomes.

Author information

  • 1Department of Oncological Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA.

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.

PMID:
19528228
[PubMed - indexed for MEDLINE]
PMCID:
PMC2725735
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk