Mechanism and regulation of DNA end resection in eukaryotes.
Mechanism and regulation of DNA end resection in eukaryotes.
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DOI：
10.3109/10409238.2016.1172552
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发表时间：
2016-05
影响因子：
6.5
通讯作者：
Symington LS
中科院分区：
文献类型：
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作者：
Symington LS
DNA双链断裂（DSB）的同源重组（HR）修复是通过末端切除（end recovery）过程中5′末端链的溶核降解来启动的。末端切除产生3′单链DNA尾，其为Rad 51催化DNA链的同源配对和交换以及激活DNA损伤检查点的底物。普遍接受的观点是末端切除通过两步机制发生。在第一步中，Sae 2/CtIP激活Mre 11-Rad 50-Xrs 2/Nbs 1（MRX/N）复合物，以内切核酸酶切割靠近断裂末端的5′-末端DNA链，在第二步中，Exo 1和/或DNA 2核酸酶延伸切除的片段，产生长的3′-ssDNA尾中间体。切除的起始使细胞通过HR修复DSB，因为长ssDNA突出端是非同源末端连接（NHEJ）的不良底物。因此，末端切除的开始已经成为修复途径选择的关键控制点。在这里，我回顾了最近的研究结束切除的机制，以及如何调节这一过程，以确保最适当的修复结果。
The repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) is initiated by nucleolytic degradation of the 5′ terminated strands in a process termed end resection. End resection generates 3′ single-stranded DNA tails, substrates for Rad51 to catalyze homologous pairing and exchange of DNA strands, and for activation of the DNA damage checkpoint. The commonly accepted view is that end resection occurs by a two-step mechanism. In the first step, Sae2/CtIP activates the Mre11-Rad50-Xrs2/Nbs1 (MRX/N) complex to endonucleolytically cleave the 5′-terminated DNA strands close to break ends, and in the second step Exo1 and/or Dna2 nucleases extend the resected tracts to produce long 3′-ssDNA-tailed intermediates. Initiation of resection commits a cell to repair a DSB by HR because long ssDNA overhangs are poor substrates for non-homologous end joining (NHEJ). Thus, the initiation of end resection has emerged as a critical control point for repair pathway choice. Here, I review recent studies on the mechanism of end resection and how this process is regulated to ensure the most appropriate repair outcome.