Kosova A A, Lavrik O I, Hodyreva S N
Mol Biol (Mosk). 2015 Jan-Feb;49(1):67-74.
Apurinic/apyrimidinic (AP) sites are some of the most frequent lesions in genomic DNA. It is widely accepted that, irrespective of their origin, AP sites are further processed by the base excision repair (BER) machinery, being the central intermediate of this process. Under special conditions, proteins, which recognize AP sites, are able to form covalent adducts with DNA. By combination of the cross-linking technique with mass-spectrometry analysis, Ku antigen (Ku)--the central player in nonhomologous end joining (NHEJ), the pathway of double-strand break (DSB) repair--was identified as a protein reactive to AP sites. Moreover, Ku was shown to be a 5'-dRP/AP lyase that acts near DSBs in NHEJ. The recent studies have demonstrated involvement of Ku in the different stages of BER. Here, Ku roles in NHEJ and BER pathways of DNA repair are overviewed.
脱嘌呤/脱嘧啶(AP)位点是基因组DNA中最常见的损伤类型之一。人们普遍认为,无论其来源如何,AP位点都会由碱基切除修复(BER)机制进一步处理,是这一过程的核心中间体。在特殊条件下,识别AP位点的蛋白质能够与DNA形成共价加合物。通过将交联技术与质谱分析相结合,Ku抗原(Ku)——非同源末端连接(NHEJ)(双链断裂(DSB)修复途径)的核心参与者——被鉴定为一种对AP位点有反应的蛋白质。此外,Ku被证明是一种5'-脱氧核糖磷酸/AP裂解酶,在NHEJ中靠近DSB处起作用。最近的研究表明Ku参与了BER的不同阶段。本文综述了Ku在DNA修复的NHEJ和BER途径中的作用。