RRC ID 12520
著者 Outwin EA, Irmisch A, Murray JM, O'Connell MJ.
タイトル Smc5-Smc6-dependent removal of cohesin from mitotic chromosomes.
ジャーナル 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.
巻・号 29(16)
ページ 4363-75
公開日 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
引用数 37
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
酵母 strains plasmids?