RNF8/RNF168信号通路在DNA损伤修复中的作用

细胞内DNA会受部分外界因素(如紫外辐射,电离辐射和化学毒素)和内部因素(如复制错误)的影响而发生损伤,包括DNA双链断裂、DNA错配和DNA交链等。DNA损伤发生后,损伤部位会被一些蛋白识别,进而招募一系列蛋白至损伤部位,形成一个修复系统。DNA双链断裂是最严重的一种DNA损伤,错误修复往往导致疾病的发生。DNA双链断裂(double strand break, DSB)后,细胞启动RNF8/RNF168信号通路进行修复。RNF8和RNF168是这条通路的枢纽蛋白;53BP和BRCA1是关键的效应蛋白,决定着DSB修复的方式;组蛋白泛素化、磷酸化和甲基化等翻译后修饰是这条通路顺利进行的基本条件;染色质重塑、泛素化酶/去泛素化酶平衡和蛋白稳定性是这条通路的主要调节方式。本综述对RNF8/RNF168信号通路进行了梳理总结,希望其能对相关研究者起到参考作用。

The Role of RNF8/RNF168 Signaling Pathway in DNA Damage Repair

DNA damage happens once it is affected by some external factors(such as ultraviolet radiation, ionizing radiation and chemical toxins) and internal factors(such as replication error). DNA damage includes DNA double strand breaks, DNA mismatch and DNA cross-linking etc. After DNA damage occurs, the site of injury is identified by a number of proteins, and then a series of proteins are recruited to the site of injury to form a repair system. DNA double strand break is the most serious type of DNA damage, and error repair often leads to the occurrence of disease.RNF8/RNF168 signaling pathway is activated for repair when cells meet with DNA double strand break(DSB). RNF8 and RNF168 are hinge proteins in this pathway, and 53 BP and BRCA1 are key effector proteins which determine the way of DSB repair. Post-translational modifications of histone such as ubiquitination, phosphorylation and methylation are the basic conditions for the smooth progress of this pathway. Chromatin remodeling, ubiquitin enzyme/deubiquitinase balance and protein stability are the main regulation types of this pathway. This review summarized the RNF8/RNF168 signaling pathway and hoped it could serve as a reference to the relevant researchers.