Ku prevents Exo1 and Sgs1-dependent resection of DNA ends in the absence of a functional MRX complex or Sae2
Ku prevents Exo1 and Sgs1-dependent resection of DNA ends in the absence of a functional MRX complex or Sae2
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DOI：
10.1038/emboj.2010.193
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发表时间：
2010-10-06
期刊：
影响因子：
11.4
通讯作者：
Symington, Lorraine S.
中科院分区：
文献类型：
--
作者：
Mimitou, Eleni P.;Symington, Lorraine S.
在这项研究中，我们调查Ku，中央非同源末端连接组件，和Mre 11-Rad 50-Xrs 2（MRX）复合物和Sae 2，末端加工因子之间的相互作用，启动5 '-3'切除双链断裂（DSB）结束的关键。我们表明，在没有端保护Ku，MRX复杂的要求被绕过和切除执行exo 1。相比之下，在Ku和Sae 2不存在的情况下，或当MRX复合物是完整的，但由于Mre 11核酸酶活性的消除而在功能上受到损害时，Exo 1和Sgs 1切除途径都有助于DSB加工。电离辐射敏感性的突变缺陷广泛切除（exo 1三角洲sgs 1三角洲）不能抑制由yku 70三角洲突变，表明Ku抑制是特定的切除术的开始。我们提供的证据表明，复制相关的DSB需要处理Sae 2修复同源重组，除非Ku是不存在的。最后，我们表明，Ku的存在加剧了在sae 2三角洲sgs 1三角洲突变体中建立的DNA末端加工缺陷，导致其致命性。The EMBO Journal（2010）29，3358-3369. doi：10.1038/daj.2010.193; 2010年8月20日在线发布
In this study, we investigate the interplay between Ku, a central non-homologous end-joining component, and the Mre11-Rad50-Xrs2 (MRX) complex and Sae2, end-processing factors crucial for initiating 5'-3' resection of double-strand break (DSB) ends. We show that in the absence of end protection by Ku, the requirement for the MRX complex is bypassed and resection is executed by Exo1. In contrast, both the Exo1 and Sgs1 resection pathways contribute to DSB processing in the absence of Ku and Sae2 or when the MRX complex is intact, but functionally compromised by elimination of the Mre11 nuclease activity. The ionizing radiation sensitivity of a mutant defective for extensive resection (exo1 Delta sgs1 Delta) cannot be suppressed by the yku70 Delta mutation, indicating that Ku suppression is specific to the initiation of resection. We provide evidence that replication-associated DSBs need to be processed by Sae2 for repair by homologous recombination unless Ku is absent. Finally, we show that the presence of Ku exacerbates DNA end-processing defects established in the sae2 Delta sgs1 Delta mutant, leading to its lethality. The EMBO Journal (2010) 29, 3358-3369. doi:10.1038/emboj.2010.193; Published online 20 August 2010