Separase-mediated cleavage of cohesin at interphase is required for DNA repair

被引:112
作者
Nagao, K
Adachi, Y
Yanagida, M
机构
[1] Kyoto Univ, Grad Sch Sci, Dept Biophys, Sakyo Ku, Kyoto 6068501, Japan
[2] Kyoto Univ, Grad Sch Biostudies, Dept Gene Mech, Sakyo Ku, Kyoto 6068501, Japan
[3] Okinawa Inst Sci & Technol, Initial Res Project, Okinawa 9042234, Japan
基金
美国国家卫生研究院; 美国国家科学基金会; 日本学术振兴会;
关键词
D O I
10.1038/nature02803
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Sister chromatids are held together by cohesins(1). At anaphase, separase is activated by degradation of its inhibitory partner, securin(2,3). Separase then cleaves cohesins(4-6), 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(7,8). Here we show that securin is essential for separase stability and also for proper repair of DNA damaged by ultraviolet, X-ray and g-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(13). 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.
引用
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页码:1044 / 1048
页数:5
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