RRC ID 883
Author Nagao K, Adachi Y, Yanagida M.
Title Separase-mediated cleavage of cohesin at interphase is required for DNA repair.
Journal Nature
Abstract Sister chromatids are held together by cohesins. At anaphase, separase is activated by degradation of its inhibitory partner, securin. Separase then cleaves cohesins, thus allowing sister chromatid separation. Fission yeast securin (Cut2) has destruction boxes and a separase (Cut1) interaction site in the amino and carboxyl terminus, respectively. Here we show that securin is essential for separase stability and also for proper repair of DNA damaged by ultraviolet, X-ray and gamma-ray irradiation. The cut2(EA2) mutant is defective in the repair of ultraviolet damage lesions, although the DNA damage checkpoint is activated normally. In double mutant analysis of ultraviolet sensitivity, checkpoint kinase chk1 (ref. 9) and excision repair rad13 (ref. 10) mutants were additive with cut2(EA2), whereas recombination repair rhp51 (ref. 11) and cohesin subunit rad21 (ref. 12) mutants were not. Cohesin was hyper-modified on ultraviolet irradiation in a Rad3 kinase-dependent way. Experiments using either mutant cohesin that cannot be cleaved by separase or a protease-dead separase provide evidence that this DNA repair function of securin-separase acts through the cleavage of cohesin. We propose that the securin-separase complex might aid DNA repair by removing local cohesin in interphase cells.
Volume 430(7003)
Pages 1044-8
Published 2004-8-26
DOI 10.1038/nature02803
PII nature02803
PMID 15329725
MeSH Amino Acid Sequence Cell Cycle Proteins / chemistry Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* Checkpoint Kinase 1 Chromosomal Proteins, Non-Histone Chromosome Segregation DNA Damage / radiation effects DNA Repair* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Endodeoxyribonucleases / genetics Endodeoxyribonucleases / metabolism Endopeptidases / genetics Endopeptidases / metabolism* Fungal Proteins Interphase* Mutation / genetics Nuclear Proteins / chemistry Nuclear Proteins / genetics Nuclear Proteins / metabolism* Phosphoproteins / chemistry Phosphoproteins / genetics Phosphoproteins / metabolism* Protein Kinases / genetics Protein Kinases / metabolism Protein Processing, Post-Translational Rad51 Recombinase Radiation Tolerance Schizosaccharomyces / cytology Schizosaccharomyces / genetics Schizosaccharomyces / metabolism* Schizosaccharomyces / radiation effects Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism* Securin Separase
IF 43.07
Times Cited 88
Yeast genomic library