The Shu complex interacts with Rad51 through the Rad51 paralogues Rad55-Rad57 to mediate error-free recombination.
The Shu complex interacts with Rad51 through the Rad51 paralogues Rad55-Rad57 to mediate error-free recombination.
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DOI：
10.1093/nar/gkt138
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发表时间：
2013-04
影响因子：
14.9
通讯作者：
Bernstein KA
中科院分区：
文献类型：
--
作者：
Godin S;Wier A;Kabbinavar F;Bratton-Palmer DS;Ghodke H;Van Houten B;VanDemark AP;Bernstein KA
酿酒酵母Shu复合物由Shu1、Shu2、Csm2和Psy3组成，以一种未知的机制促进无差错同源重组（HR）。最近对两种Shu蛋白Csm2和Psy3的结构分析表明，这两种蛋白是Rad51的类似物，并介导该复合物的DNA结合。我们在体外表明，Csm2-Psy3异源二聚体优先结合合成分叉DNA或3 ' -DNA悬垂底物，类似于体内HR过程中使用的结构。我们发现Csm2与Rad51、Rad51同源物、Rad55-Rad57异源二聚体相互作用，Shu复合体与Rad55-Rad57在相同的作用群中起作用。重要的是，Csm2与Rad51的相互作用依赖于Rad55，而Csm2与Rad55的相互作用独立于Rad51。与含有Rad51类似物的Shu配合物一致，Csm2的甲基磺酸敏感性在较低的温度下加剧。此外，Csm2和Psy3是Rad55在DNA损伤后有效募集到DNA修复病灶所必需的。最后，我们观察到Shu复合物优先促进rad51依赖的同源重组，而不是rad51不依赖的修复。我们的数据表明，Csm2-Psy3将Shu复合物招募到HR底物中，在那里它通过Rad55-Rad57与Rad51相互作用，刺激Rad51丝的组装和稳定性，促进无错误修复。
The Saccharomyces cerevisiae Shu complex, consisting of Shu1, Shu2, Csm2 and Psy3, promotes error-free homologous recombination (HR) by an unknown mechanism. Recent structural analysis of two Shu proteins, Csm2 and Psy3, has revealed that these proteins are Rad51 paralogues and mediate DNA binding of this complex. We show in vitro that the Csm2–Psy3 heterodimer preferentially binds synthetic forked DNA or 3′-DNA overhang substrates resembling structures used during HR in vivo. We find that Csm2 interacts with Rad51 and the Rad51 paralogues, the Rad55–Rad57 heterodimer and that the Shu complex functions in the same epistasis group as Rad55–Rad57. Importantly, Csm2’s interaction with Rad51 is dependent on Rad55, whereas Csm2’s interaction with Rad55 occurs independently of Rad51. Consistent with the Shu complex containing Rad51 paralogues, the methyl methanesulphonate sensitivity of Csm2 is exacerbated at colder temperatures. Furthermore, Csm2 and Psy3 are needed for efficient recruitment of Rad55 to DNA repair foci after DNA damage. Finally, we observe that the Shu complex preferentially promotes Rad51-dependent homologous recombination over Rad51-independent repair. Our data suggest a model in which Csm2–Psy3 recruit the Shu complex to HR substrates, where it interacts with Rad51 through Rad55–Rad57 to stimulate Rad51 filament assembly and stability, promoting error-free repair.
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影响因子：
14.9
作者：
Colavito S;Macris-Kiss M;Seong C;Gleeson O;Greene EC;Klein HL;Krejci L;Sung P
通讯作者：
Sung P
影响因子：
5.3
作者：
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影响因子：
10.5
作者：
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通讯作者：
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作者：
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通讯作者：
Rothstein R
影响因子：
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作者：
Karpenshif, Yoav;Bernstein, Kara A.
通讯作者：
Bernstein, Kara A.