Non-homologous DNA end joining and alternative pathways to double-strand break repair.

Non-homologous DNA end joining and alternative pathways to double-strand break repair.
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DOI:
10.1038/nrm.2017.48
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发表时间:
2017-08
期刊:
Nature reviews. Molecular cell biology
影响因子:
--
通讯作者:
Lieber MR
Lieber MR
中科院分区:
其他
文献类型:
--
作者:
Chang HHY;Pannunzio NR;Adachi N;Lieber MR

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DNA双链断裂(DSB)是最危险的DNA损伤类型,因为它们会导致大的染色体区域丢失。在所有哺乳动物细胞中,在整个细胞周期中发生的DSB主要通过非同源DNA末端连接(NHEJ)途径修复。NHEJ缺陷导致对电离辐射敏感和淋巴细胞消融。NHEJ途径利用以灵活方式识别、切除、切割和连接DNA末端的蛋白质。这种灵活性允许NHEJ在广泛的DNA末端构型上发挥作用,所得到的修复的DNA连接通常包含突变。在这篇评论中,我们讨论了有关不同NHEJ蛋白相对参与各种DNA末端构型修复的最新发现。我们还讨论了分流的DNA末端修复的辅助途径的替代末端连接(a-EJ)或单链退火(SSA)和人类疾病的相关性,这些不同的途径。
DNA double-strand breaks (DSBs) are the most dangerous type of DNA damage because they can result in the loss of large chromosomal regions. In all mammalian cells, DSBs that occur throughout the cell cycle are repaired predominantly by the non-homologous DNA end joining (NHEJ) pathway. Defects in NHEJ result in sensitivity to ionizing radiation and the ablation of lymphocytes. The NHEJ pathway utilizes proteins that recognize, resect, polymerize and ligate the DNA ends in a flexible manner. This flexibility permits NHEJ to function on a wide range of DNA-end configurations, with the resulting repaired DNA junctions often containing mutations. In this Review, we discuss the most recent findings regarding the relative involvement of the different NHEJ proteins in the repair of various DNA-end configurations. We also discuss the shunting of DNA-end repair to the auxiliary pathways of alternative end joining (a-EJ) or single-strand annealing (SSA) and the relevance of these different pathways to human disease.
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