Repair Pathway Choices and Consequences at the Double-Strand Break.
Repair Pathway Choices and Consequences at the Double-Strand Break.
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DOI：
10.1016/j.tcb.2015.07.009
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发表时间：
2016-01
影响因子：
19
通讯作者：
D'Andrea AD
中科院分区：
文献类型：
--
作者：
Ceccaldi R;Rondinelli B;D'Andrea AD
DNA双链断裂（DSB）是威胁基因组完整性的细胞毒性病变。不能修复DSB会产生有害的后果，包括基因组不稳定和细胞死亡。事实上，DSB的错误修复可导致不适当的末端连接事件，这通常是由于染色体易位引起的致癌转化的基础。通常，细胞采用两种主要机制来修复DSB：同源重组（HR）和经典的非同源末端连接（C-NHEJ）。此外，替代的易错DSB修复途径，即替代末端连接（alt-EJ）和单链退火（SSA），最近已被证明在许多不同的条件下运作，并有助于基因组重排和致癌转化。在这里，我们审查的机制，调节DSB修复途径的选择，以及潜在的相互关系之间的HR和退火依赖性的易错DSB修复途径。
DNA double-strand breaks (DSBs) are cytotoxic lesions that threaten genomic integrity. Failure to repair a DSB has deleterious consequences, including genomic instability and cell death. Indeed, misrepair of DSBs can lead to inappropriate end-joining events, which commonly underlie oncogenic transformation due to chromosomal translocations. Typically, cells employ two main mechanisms to repair DSBs: homologous recombination (HR) and classical nonhomologous end joining (C-NHEJ). In addition, alternative error-prone DSB repair pathways, namely alternative end joining (alt-EJ) and single-strand annealing (SSA), have been recently shown to operate in many different conditions and to contribute to genome rearrangements and oncogenic transformation. Here, we review the mechanisms regulating DSB repair pathway choice, together with the potential interconnections between HR and the annealing-dependent error-prone DSB repair pathways.