DNA损伤修复的单分子水平研究进展

外源或内源的DNA损伤在生物体内持续发生。DNA损伤修复的缺陷与很多疾病甚至癌症等息息相关，而生物细胞进化出一系列精密的修复机制以耐受或切除这些损伤。单分子技术区别于常规的生化、分子生物学等手段，可以在体外和活细胞内研究DNA修复相关生物分子的动态反应特征，从而对DNA修复机制进行更充分的剖析。文章围绕常见的DNA损伤及其修复类型，阐述了近年来利用原子力显微镜、磁镊、光镊等单分子操控技术，以及全内反射荧光显微镜、光激活定位显微镜和超分辨显微示踪等单分子荧光成像技术在DNA修复机制研究中取得的进展，梳理了利用单分子技术解决的长期存在的关于DNA修复难题，并展望了单分子技术联合其他交叉学科技术在研究DNA修复机制方面的前景。

Advances in single-molecule investigation on DNA damage repair

Exogenous or endogenous DNA damages occur continuously in all domains of organisms. Defects in DNA damage repair are closely related to many serious diseases even cancers. Along with evolution, biological cells have developed a series of sophisticated repair pathways to remove or tolerate these damages. Different from conventional biochemical and molecular biology methods, cutting-edge single-molecule technologies are employed to investigate the dynamic functionality of DNA repairrelated biomolecules in vitro and in living cells, which is beneficial to understand more adequately the mechanisms of DNA repair pathways. This review focuses on the common types of DNA damage and repair pathways, and describes single-molecule manipulation techniques such as atomic force microscopy, magnetic tweezers, optical tweezers, and single-molecule fluorescence imaging technologies such as total internal reflection fluorescence microscopy, photoactivation localization microscopy, and superresolution tracking microscopy. The researches of DNA repair mechanism in recent years have been presented as well. The longstanding problems about DNA repair studied via single-molecule technology are sorted out. In the end, we prospected single-molecule technology and other interdisciplinary technologies in the investigation of DNA repair mechanism.