The Mre11/Rad50/Nbs1 complex functions in resection-based DNA end joining in Xenopus laevis.
The Mre11/Rad50/Nbs1 complex functions in resection-based DNA end joining in Xenopus laevis.
复制标题
MRE11/RAD50/NBS1复合物在基于切除的DNA末端连接在Xenopus laevis中。
DOI：
10.1093/nar/gkp905
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发表时间：
2010-01
影响因子：
14.9
通讯作者：
Lindsay HD
中科院分区：
文献类型：
--
作者：
Taylor EM;Cecillon SM;Bonis A;Chapman JR;Povirk LF;Lindsay HD
DNA双链断裂（DSBs）的修复对于维持基因组的完整性至关重要。在高等真核生物中，DNA dsb主要通过非同源末端连接（NHEJ）修复，但DNA末端也可以通过另一种容易出错的机制连接，称为微同源介导的末端连接（MMEJ）。在MMEJ中，DNA断裂的修复是通过微同源区域的退火介导的，并且总是与断裂位点的缺失有关。在出芽酵母中，Mre11/Rad5/Xrs2复合体已被证明在经典的NHEJ和MMEJ中发挥作用，但类似的Mre11/ RAD50/NBS1 （MRN）复合体是否参与高等真核生物的末端连接尚不确定。本研究表明，在非洲爪蟾卵提取物中，经典的dna - pk依赖性NHEJ不需要MRN复合物。然而，XMRN复合体对于不匹配DNA末端的基于切除的末端连接是必需的。这种依赖xmrn的末端连接过程不依赖于NHEJ的核心成分Ku70和DNA-PK，相对于经典的NHEJ发生延迟动力学，并在微同源位点进行修复。这些数据表明了X. laevis MRN复合体在MMEJ中的作用。
The repair of DNA double-strand breaks (DSBs) is essential to maintain genomic integrity. In higher eukaryotes, DNA DSBs are predominantly repaired by non-homologous end joining (NHEJ), but DNA ends can also be joined by an alternative error-prone mechanism termed microhomology-mediated end joining (MMEJ). In MMEJ, the repair of DNA breaks is mediated by annealing at regions of microhomology and is always associated with deletions at the break site. In budding yeast, the Mre11/Rad5/Xrs2 complex has been demonstrated to play a role in both classical NHEJ and MMEJ, but the involvement of the analogous MRE11/RAD50/NBS1 (MRN) complex in end joining in higher eukaryotes is less certain. Here we demonstrate that in Xenopus laevis egg extracts, the MRN complex is not required for classical DNA-PK-dependent NHEJ. However, the XMRN complex is necessary for resection-based end joining of mismatched DNA ends. This XMRN-dependent end joining process is independent of the core NHEJ components Ku70 and DNA-PK, occurs with delayed kinetics relative to classical NHEJ and brings about repair at sites of microhomology. These data indicate a role for the X. laevis MRN complex in MMEJ.
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