ADP-核糖基化可逆修饰在DNA损伤应答及癌症治疗中的研究进展

Progress in reversible ADP-ribosylation modification in DNA damage repair and cancer treatment

细胞基因组DNA遭受到各种内外源因素的攻击可以诱发多种类型的DNA损伤.DNA损伤应答系统(DNA damage response,DDR)能及时识别、修复受损的DNA,维持基因组稳定性,避免肿瘤等多种疾病发生.DDR受到多种蛋白质翻译后修饰的严格调控,ADP-核糖基化(ADP-ribosylation)是其中最为重要的修饰类型之一.ADP-核糖基化是一种动态可逆的翻译后修饰,ADP-核糖基化与去核糖基化之间保持动态平衡,精密调控DNA损伤应答过程.鉴于ADP-核糖基化在DNA损伤修复中的独特功能,靶向这一可逆过程的抑制剂已被开发或有望作为一类用于癌症治疗的靶向药物.本文就ADP-核糖基化可逆修饰在DNA损伤修复及癌症治疗中的研究进展进行综述.

Cellular genomic DNA is attacked by various internal and external stimuli,inducing multiple types of DNA damage.DNA damage response(DDR)can hastily repair DNA damage,maintain genome stability,and avoid tumors and other diseases.DDR is regulated by diverse protein posttranslational modifications.ADP-ribosylation is one of the most important modifications in DDR.ADPribosylation is a dynamic and reversible posttranslational modification.The dynamic balance between ADP-ribosylation and de-ADPribosylation precisely regulates DDR.Given the unique function of ADP-ribosylation in DNA damage repair,inhibitors targeting this reversible process have been developed and are expected to be a new class of chemotherapeutics for cancer treatment.This review introduces the research progress of reversible ADP-ribosylation modification in DNA damage repair and cancer treatment.