Reference - Detail
| RRC ID | 12520 |
|---|---|
| Author | Outwin EA, Irmisch A, Murray JM, O'Connell MJ. |
| Title | Smc5-Smc6-dependent removal of cohesin from mitotic chromosomes. |
| Journal | Mol Cell Biol |
| 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. |
| Volume | 29(16) |
| Pages | 4363-75 |
| Published | 2009-8-1 |
| DOI | 10.1128/MCB.00377-09 |
| PII | MCB.00377-09 |
| PMID | 19528228 |
| PMC | PMC2725735 |
| MeSH | Animals Cell Cycle / physiology Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* Chromosomal Proteins, Non-Histone / genetics Chromosomal Proteins, Non-Histone / metabolism* Chromosome Segregation* Chromosomes / metabolism* DNA Damage DNA Repair Endopeptidases / genetics Endopeptidases / metabolism Humans Mitosis / physiology* Nuclear Proteins / genetics Nuclear Proteins / metabolism Phosphoproteins / genetics Phosphoproteins / metabolism Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Schizosaccharomyces / genetics Schizosaccharomyces / metabolism* Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism* Separase |
| IF | 3.611 |
| Times Cited | 37 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| Resource | |
| Yeast | strains plasmids? |