RNA甲基化修饰调控DNA损伤修复过程及其在肿瘤耐药中的作用

Regulation of RNA methylation modifications during DNA damage repair and their roles in tumor drug resistance

DNA损伤修复是指纠正DNA两条单链间错配的碱基、清除DNA链上受损的碱基、恢复DNA正常结构的过程。细胞内存在多种机制来应对不同类型的DNA损伤,同源重组修复便是重要的修复机制之一。在同源重组修复过程中,RNA的合成发挥着重要作用,而RNA甲基化修饰作为一个普遍存在于真核细胞中的调控机制,也参与了这一复杂的修复过程。肿瘤发生过程中普遍存在RNA甲基化修饰失调导致的DNA损伤累积,从而引起肿瘤的恶性转化。此外,RNA甲基化修饰还可以影响放化疗后细胞对DNA损伤的修复能力,使肿瘤细胞的放化疗敏感性发生改变,进而影响治疗效果。本文综述了目前已知的不同类型RNA甲基化修饰在DNA损伤修复过程中的作用,并进一步分析RNA甲基化修饰介导的DNA损伤修复异常在肿瘤临床诊断、预后判断和作为治疗靶点等方面的应用前景。

DNA damage repair refers to the process of correcting mismatches between bases on two single DNA strands,removing damaged bases from the DNA chain,and restoring the normal structure of DNA.There are various mechanisms within cells to address different types of DNA damage,and homologous recombination repair is one of the significant repair mechanisms.In the process of homologous recombination repair,the synthesis of new RNA plays a crucial role,and RNA methylation modification,as a ubiquitous regulatory mechanism in eukaryotic cells,also participates in this complex repair process.In the process of tumor development,there is a common accumulation of DNA damage caused by the dysregulation of RNA methylation modifications,resulting in the malignant transformation of tumors.Additionally,RNA methylation modifications can also affect the repair capacity of cells after radiotherapy and chemotherapy,causing changes in the sensitivity of tumor cells to radiotherapy and chemotherapy,thereby affecting the treatment effect.In the current review,we summarized the types of RNA methylation modifications and their roles in the process of DNA damage repair,and further discussed their application prospects in the clinical diagnosis,prognosis and therapeutic targets of tumors.