Cohesin Releases DNA through Asymmetric ATPase-Driven Ring Opening

被引：62

作者：

Elbatsh, Ahmed M. O. ^{[1
]}

Haarhuis, Judith H. I. ^{[1
]}

Petela, Naomi ^{[2
]}

Chapard, Christophe ^{[2
]}

Fish, Alexander ^{[3
]}

Celie, Patrick H. ^{[3
]}

Stadnik, Magda ^{[3
]}

Ristic, Dejan ^{[4
,5
]}

Wyman, Claire ^{[4
,5
]}

Medema, Rene H. ^{[1
]}

Nasmyth, Kim ^{[2
]}

Rowland, Benjamin D. ^{[1
]}

机构：

[1] Netherlands Canc Inst, Div Cell Biol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands

[2] Univ Oxford, Dept Biochem, S Parks Rd, Oxford OX1 3QU, England

[3] Netherlands Canc Inst, Div Biochem, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands

[4] Erasmus Univ, Med Ctr, Dept Genet, Canc Genom Netherlands, NL-3000 CA Rotterdam, Netherlands

[5] Erasmus Univ, Med Ctr, Dept Radiat Oncol, NL-3000 CA Rotterdam, Netherlands

来源：

MOLECULAR CELL | 2016年 / 61卷 / 04期

基金：

英国惠康基金;

关键词：

SISTER-CHROMATID COHESION; WAPL CONTROLS; ESTABLISHMENT; ACETYLATION; CHROMOSOMES; BINDING; SMC3; ASSOCIATION; HYDROLYSIS; MECHANISM;

D O I：

10.1016/j.molcel.2016.01.025

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cohesin stably holds together the sister chromatids from S phase until mitosis. To do so, cohesin must be protected against its cellular antagonist Wapl. Eco1 acetylates cohesin's Smc3 subunit, which locks together the sister DNAs. We used yeast genetics to dissect how Wapl drives cohesin from chromatin and identified mutants of cohesin that are impaired in ATPase activity but remarkably confer robust cohesion that bypasses the need for the cohesin protectors Eco1 in yeast and Sororin in human cells. We uncover a functional asymmetry within the heart of cohesin's highly conserved ABC-like ATPase machinery and find that both ATPase sites contribute to DNA loading, whereas DNA release is controlled specifically by one site. We propose that Smc3 acetylation locks cohesin rings around the sister chromatids by counteracting an activity associated with one of cohesin's two ATPase sites.

引用

页码：575 / 588

页数：14

共 23 条

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