端粒结合蛋白在端粒复制与损伤修复中的作用  

Role of Telomere Binding Proteins in Telomere Replication and Damage Repair

作　　者：宗欢欢 侯凯龙 郭鑫 罗瑛 贾舒婷 ZONG Huan-Huan;HOU Kai-Long;GUO Xin;LUO Ying;JIA Shu-Ting(Laboratory of Molecular Genetics of Aging and Tumor,Medical School,Kunming University of Science and Technology,Kunming 650224,China;Guizhou Provincial Key Laboratory of Pathogenesis&Drug Development on Common Chronic Diseases,School of Basic Medicine,Guizhou Medical University,Guiyang 550025,China)

机构地区：[1]昆明理工大学医学院,衰老与肿瘤分子遗传学实验室,昆明650224 [2]贵州医科大学基础医学院,贵州省常见慢性疾病发病机制及药物研究重点实验室,贵阳550025

出　　处：《生物化学与生物物理进展》2021年第12期1448-1455,共8页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(81760262);云南省应用基础研究计划(2019FB109);云南省“万人计划”青年拔尖人才专项(YNWRQNBJ-2019-240)资助项目。

摘　　要：端粒位于真核细胞线性染色体末端,正常的端粒长度与结构对于细胞基因组稳定的维持有重要作用.端粒DNA序列的高度重复性使其容易形成一些特殊的二级结构,相比染色体其他位置更难复制.结合在端粒上的Shelterin蛋白复合体由六个端粒结合蛋白组成,该复合体可以通过抑制端粒处异常DNA损伤修复途径的激活维持端粒的稳定.此外,近几年的研究显示,Shelterin蛋白复合体还具有调控功能异常端粒的DNA修复途径选择,参与端粒的复制功能.因此,本文就最近发现的Shelterin蛋白复合体成员调控的端粒处DNA修复及参与的端粒复制过程进行综述.Telomeres localize at the ends of all linear chromosomes of eukaryotic cells to preserve genome integrity and cell survival.The highly repetitive telomeric sequences can easily fold into specific secondary structures that are difficult to replicate,resulting in increased replication stress.Telomeric repeats are bound by Shelterin complex,which consist of six telomere-specific proteins,and function to protect telomeres by preventing aberrant DNA damage response activation.Recently,it was shown that Shelterin components can also regulate the choice of DNA repair pathways in dysfunctional telomeres,and participate in telomere replication.In this review,we summarize how the secondary structures in telomere are stabilized/removed by Shelterin to ensure repilication proceeding.Moreover,we also discussed the inhibition of DNA repair at telomeres by Shelterin and how Shelterin mediates the repair pathway choice of dysfunctional telomeres.There is still much room to explore on the coordination between telomere protection,replication and regulation of telomeric DNA repair.Hopefully,the further exploration of telomere maintenance mechanism can provide new ideas and therapeutic strategies for telomere-related diseases such as aging and cancer.

关 键 词：端粒 Shelterin蛋白复合体 DNA损伤修复途径 

分 类 号：Q71[生物学—分子生物学] R394.3[医药卫生—医学遗传学]