DNA双链断裂的非同源末端连接修复

细胞内普遍存在的DNA双链断裂(DSB)可通过同源重组(HR)或非同源末端连接(NHEJ)修复。由于HR仅在存在相同染色体作为模板的时候进行,因此,NHEJ通常为主要的修复方式。在NHEJ中,DSB末端首先由Ku识别,接着由核酸酶、聚合酶在Ku与DNA-PKcs协助下加工,并由连接酶IVXRCC4-XLF连接。NHEJ底物类型多样,末端的修复常包含反复加工的过程,导致修复产物通常无法复原损伤前的序列。虽然无法确保准确修复DNA,NHEJ仍对维持基因组的稳定性具有重要的意义。对NHEJ的研究有助于理解癌症的发生机制并将促进癌症的治疗。

Role of nonhomologous end joining pathway in the repair of DNA double-strand breaks

As a deleterious but common form of DNA damage, DNA double-strand breaks （DSB） can be repaired by both homologous recombination （HR） and nonhomologous end joining （NHEJ） pathways. As HR takes place only when an intact homologous chromatin is prepared as a template, NHEJ is the primary pathway to repair DSB. DSB is initially recognized by Ku. With the help of DNA-PKcs, Ku recruits nucleases and polymerases for end processing and ligase IV-XRCC4-XLF for the final ligation step. Although the structural diversity of break ends and iterative processing of DNA ends together make NHEJ an error-prone pathway, it plays a significant role in the maintenance of genome stability. Research on the mechanism of NHEJ will shed light on the mechanism of oncogenesis so as to develop better strategies for cancer therapy.