DNA损伤修复机制的研究进展

摘要

细胞遗传物质稳定性受自身与外界多种条件影响,可形成多种类型DNA损伤,如DNA烷基化、氧化、错配、成环、断裂、非典型结构等.这些受损DNA扰乱细胞稳态及动态平衡,引起基因突变、染色体畸形,甚至细胞和生物退化、老化、死亡等.人体通过识别DNA损伤位点,激活一系列生化通路,协调DNA复制与转录,使损伤DNA得以修复,维持机体相对独立、稳定.放射线引起肿瘤细胞DNA损伤同时,也启动DNA损伤应答,其中碱基切除修复、核苷酸切除修复、错配修复、双链断裂修复和跨损伤合成修复起关键作用,是细胞照射后DNA修复的主要途径,其功能异常可引起肿瘤放射敏感性差异.本文总结近年国内外DNA损伤修复方面的研究成果,着重阐述DNA损伤修复类型及分子机制,旨在促进读者对该领域重要意义的理解,为探索DNA损伤修复通路在肿瘤治疗中的应用提供理论基础.%The stability of cell genetic material is influenced by a variety of factors, both internal and external, which can cause various types of DNA damage, such as DNA alkylation, oxidation, mismatching, loop structure, atypical DNA structure, single-strand break, and double-strand break.These DNA damages disrupt cellular homeostasis and dynamic equilibrium, which cause gene mutations, chromosomal abnormalities, and even degradation, aging, and death at different biological levels.By searching and identifying DNA damage sites, the cell activates a series of biochemical pathways, coordinates the progress of DNA replication and transcription, and then repairs the DNA damage.In this way, the cell maintains its independence and stability.While radiotherapy plays a role in eliminating tumors by DNA damages, it also initiates DNA damage responses.Among the responses, base excision repair, nucleotide excision repair, mismatch repair, double-strand break repair, and post-translesion synthesis repair play a key role in repairing the damages.The dysfunction of these repair pathways will cause differences in tumor radiation sensitivity.This paper summarizes recent research results in DNA damage repair, and focuses on the types of DNA damage and their repair mechanisms, so as to promote the understanding of the great significance of this field and to provide a theoretical basis for exploring the application of DNA damage repair pathways in tumor therapy.