Sirtuin家族与DNA损伤修复

Sirtuin Family and DNA Damage Repair

DNA损伤的发生与积累是造成细胞功能紊乱的根本原因,也是引起衰老与肿瘤等疾病发生的关键事件。为维持机体自身遗传物质的完整性与稳定性,生物体内拥有多种针对不同类型DNA损伤的修复方式。Sirtuin蛋白是一组NAD+依赖的、高度保守的组蛋白去乙酰化酶,可通过去乙酰化作用调节众多底物蛋白质的表达、活性与稳定性。近来的研究显示,DNA损伤修复途径的多个关键蛋白质是Sirtuin的下游底物。Sirtuin蛋白通过调节同源重组修复、非同源末端修复、核苷酸切除修复等途径中的核心蛋白质参与修复包括双链断裂(double stranded breakes,DSBs)在内的多种DNA损伤类型,从而在维持基因组稳定性、寿命以及细胞能量代谢调节等一系列生物学作用中发挥至关重要的作用。本综述将介绍近年来Sirtuin与DNA损伤修复的研究进展。

The occurrence and accumulation of DNA damage is the leading cause of cell dysfunctions,which ultimately induces the development of aging and tumor. To maintain the genomic integrity and stability,the cells evolve multiple DNA repair pathways against diverse types of DNA damage. Sirtuins are the members of NAD＋dependent,conserved HDACs（ histone deacetylase） family,which direct impact the expression of target genes and the function of target proteins. Recent studies have demonstrated that various key proteins involved in the DNA repair pathways,were direct substrates of sirtuins. Sirtuins have been established to influence the repair of various types of DNA damage including double stranded breaks（ DSBs）,through regulation the substrates involved in homologous recombination（ HR）,non-homologous end joining（ NHEJ）,nucleotide excision repair（ NER）,etc. Therefore,sirtuins play a crucial role in maintaining the genomic integrity and stability,regulating the lifespan and cell energy metabolism. We herein summarized the recent advances of the relationship between sirtuins and DNA damage repair.