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.

中文翻译：

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非同源DNA末端连接和双链断裂修复的替代途径。

DNA双链断裂（DSB）是最危险的DNA损伤类型，因为它们可能导致大染色体区域的丢失。在所有哺乳动物细胞中，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中的缺陷会导致对电离辐射和淋巴细胞消融的敏感性。NHEJ途径利用以灵活方式识别，切除，聚合和连接DNA末端的蛋白质。这种灵活性使NHEJ可以在广泛的DNA末端构型上发挥作用，从而导致修复后的DNA连接通常含有突变。在这篇综述中，我们讨论了有关不同NHEJ蛋白在各种DNA末端构型修复中的相对参与的最新发现。