Biochemical mechanism of DSB end resection and its regulation.
Biochemical mechanism of DSB end resection and its regulation.
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DOI：
10.1016/j.dnarep.2015.04.015
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发表时间：
2015-08
期刊：
影响因子：
3.8
通讯作者：
Sung P
中科院分区：
文献类型：
--
作者：
Daley JM;Niu H;Miller AS;Sung P
细胞中的 DNA 双链断裂 (DSB) 可以经历溶核降解，产生长 3' 单链 DNA 尾。这个过程被称为 DNA 末端切除，它的发生有效地通过同源重组进行断裂修复，这需要从完整的同源供体 DNA 序列中获取遗传信息。由催化切除的核酸酶的鉴定所推动的最新进展揭示了复杂的功能冗余、互连性和调节层。在这里，我们回顾了该领域的现状，重点是仍有待回答的主要问题。讨论的主题包括如何通过在断裂端附近引入核酸内切切口来启动切除、在此类模型中保守的 MRE11 复合物与 Sae2/CtIP 结合的分子机制、BRCA1 和 53BP1 在调节哺乳动物细胞中切除启动中的作用、染色质在切除过程中的影响以及新因素的潜在作用。
DNA double-strand breaks (DSBs) in cells can undergo nucleolytic degradation to generate long 3′ single-stranded DNA tails. This process is termed DNA end resection, and its occurrence effectively commits to break repair via homologous recombination, which entails the acquisition of genetic information from an intact, homologous donor DNA sequence. Recent advances, prompted by the identification of the nucleases that catalyze resection, have revealed intricate layers of functional redundancy, interconnectedness, and regulation. Here, we review the current state of the field with an emphasis on the major questions that remain to be answered. Topics addressed will include how resection initiates via the introduction of an endonucleolytic incision close to the break end, the molecular mechanism of the conserved MRE11 complex in conjunction with Sae2/CtIP within such a model, the role of BRCA1 and 53BP1 in regulating resection initiation in mammalian cells, the influence of chromatin in the resection process, and potential roles of novel factors.