Regulatory control of DNA end resection by Sae2 phosphorylation.
Regulatory control of DNA end resection by Sae2 phosphorylation.
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DOI：
10.1038/s41467-018-06417-5
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发表时间：
2018-10-01
影响因子：
16.6
通讯作者：
Cejka P
中科院分区：
文献类型：
--
作者：
Cannavo E;Johnson D;Andres SN;Kissling VM;Reinert JK;Garcia V;Erie DA;Hess D;Thomä NH;Enchev RI;Peter M;Williams RS;Neale MJ;Cejka P
DNA末端切除在DNA双链断裂修复途径的选择中起着关键作用。切除的DNA末端对末端连接机制是难治的，而是被引导到同源定向修复。使用生物化学，遗传学和成像方法，我们表明，磷酸化的酿酒酵母Sae 2控制其能力，以促进Mre 11-Rad 50-Xrs 2（MRX）核酸酶启动切除封闭的DNA末端至少有两种不同的机制。首先，DNA损伤和细胞周期依赖性磷酸化导致Sae 2四聚化。其次，独立地，Sae 2的保守C-末端结构域的磷酸化是其与Rad 50的物理相互作用的先决条件，这对于促进MRX内切核酸酶也是至关重要的。这种相互作用的缺乏解释了在减数分裂重组过程中Spo 11结合的DNA末端的加工缺陷的rad 50 S突变体的表型。我们的研究结果定义了磷酸化如何控制DNA末端切除的起始，从而在关键的DNA双链断裂修复机制之间进行选择。先前已经确定酵母和人类中的DNA末端切除在CDK控制下。在这里，作者解释了磷酸化如何调节Sae 2（人类CtIP的酵母直系同源物）促进DNA末端切除的能力。
DNA end resection plays a critical function in DNA double-strand break repair pathway choice. Resected DNA ends are refractory to end-joining mechanisms and are instead channeled to homology-directed repair. Using biochemical, genetic, and imaging methods, we show that phosphorylation of Saccharomyces cerevisiae Sae2 controls its capacity to promote the Mre11-Rad50-Xrs2 (MRX) nuclease to initiate resection of blocked DNA ends by at least two distinct mechanisms. First, DNA damage and cell cycle-dependent phosphorylation leads to Sae2 tetramerization. Second, and independently, phosphorylation of the conserved C-terminal domain of Sae2 is a prerequisite for its physical interaction with Rad50, which is also crucial to promote the MRX endonuclease. The lack of this interaction explains the phenotype of rad50S mutants defective in the processing of Spo11-bound DNA ends during meiotic recombination. Our results define how phosphorylation controls the initiation of DNA end resection and therefore the choice between the key DNA double-strand break repair mechanisms. It has previously been established that DNA end resection in yeast and in humans is under CDK control. Here the authors explain how phosphorylation regulates the capacity of Sae2 — the yeast orthologue of human CtIP — to promote DNA end resection.
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影响因子：
16.8
作者：
Andres, Sara N.;Appel, C. Denise;Westmoreland, James W.;Williams, Jessica S.;Nguyen, Yvonne;Robertson, Patrick D.;Resnick, Michael A.;Williams, R. Scott
通讯作者：
Williams, R. Scott
DOI：
10.1073/pnas.1503331112
发表时间：
2015-04-14
影响因子：
11.1
作者：
Chen, Huan;Donnianni, Roberto A.;Symington, Lorraine S.
通讯作者：
Symington, Lorraine S.
影响因子：
64.8
作者：
Garcia V;Gray S;Allison RM;Cooper TJ;Neale MJ
通讯作者：
Neale MJ
影响因子：
16.8
作者：
通讯作者：
--
影响因子：
4.8
作者：
Clerici, M;Mantiero, D;Longhese, MP
通讯作者：
Longhese, MP