The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway.
The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway.
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DOI：
10.1146/annurev.biochem.052308.093131
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发表时间：
2010
影响因子：
16.6
通讯作者：
Lieber MR
中科院分区：
文献类型：
--
作者：
Lieber MR
双链DNA断裂是真核细胞中常见的事件，其修复主要有两种途径：同源重组和非同源DNA末端连接（NHEJ）。DSB的不同原因导致必须修复的DNA末端的不同化学性质。在整个NHEJ进化过程中，NHEJ途径的酶在它们可以作用的DNA末端底物构型的范围内表现出显著程度的结构耐受性。在脊椎动物细胞中，NHEJ的核酸酶、聚合酶和连接酶是它们各自类别中最具机械灵活性和多功能的酶。与更明确损伤的修复途径不同，NHEJ修复酶反复作用，以任何顺序作用，并且可以在连接的两个DNA末端中的每一个处彼此独立地发挥作用。NHEJ不仅对于如染色体易位中的病理性DSB的修复至关重要，而且对于V（D）J重组和类别转换重组期间产生的生理性DSB的修复也至关重要。因此，缺乏正常NHEJ的患者不仅对电离辐射敏感，而且严重免疫缺陷。
Double-strand DNA breaks are common events in eukaryotic cells, and there are two major pathways for repairing them: homologous recombination and nonhomologous DNA end joining (NHEJ). The diverse causes of DSBs result in a diverse chemistry of DNA ends that must be repaired. Across NHEJ evolution, the enzymes of the NHEJ pathway exhibit a remarkable degree of structural tolerance in the range of DNA end substrate configurations upon which they can act. In vertebrate cells, the nuclease, polymerases and ligase of NHEJ are the most mechanistically flexible and multifunctional enzymes in each of their classes. Unlike repair pathways for more defined lesions, NHEJ repair enzymes act iteratively, act in any order, and can function independently of one another at each of the two DNA ends being joined. NHEJ is critical not only for the repair of pathologic DSBs as in chromosomal translocations, but also for the repair of physiologic DSBs created during V(D)J recombination and class switch recombination. Therefore, patients lacking normal NHEJ are not only sensitive to ionizing radiation, but also severely immunodeficient.
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