Mutual inhibition between miR-34a and SIRT1 contributes to regulation of DNA double-strand break repair  

作　　者：XU Miao LU Lu MAO BeiBei Lü Xiang WU XueSong LI Lei LIU DePei 

机构地区：[1]National Laboratory of Medical Molecular Biology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences & Peking Union Medical College

出　　处：《Chinese Science Bulletin》2013年第9期979-985,共7页

基　　金：supported by the National Basic Research Program of China (2011CB965203);the National Natural Science Foundation of China (31030026 and 31021091)

摘　　要：DNA double-strand breaks are repaired through either non-homologous end joining(NHEJ) or homologous recombination repair(HRR) pathway.The well-characterized regulatory mechanisms of double-strand break repair(DSBR) are mainly found at the level of complicated repair protein interactions and modifications.Regulation of DSBR at the transcriptional level was also reported.In this study,we found that DSBR can be regulated by miR-34a at the post-transcriptional level.Specifically,miR-34a,which can be activated by DNA damages,represses DSBR activities by impairing both NHEJ and HRR pathways in cultured cells.The repression is mainly through targeting the critical DSBR promoting factor SIRT1,as ectopically expressed SIRT1 without 3'-UTR can rescue the inhibitory roles of miR-34a on DSBR.Further studies demonstrate that SIRT1 conversely represses miR-34a expression.Taken together,our data show that miR-34a is a new repressor of DSBR and the mutual inhibition between miR-34a and SIRT1 may contribute to regulation of DNA damage repair.DNA double-strand breaks are repaired through either non-homologous end joining （NHEJ） or homologous recombination repair （HRR） pathway. The well-characterized regulatory mechanisms of double-strand break repair （DSBR） axe mainly found at the level of complicated repair protein interactions and modifications. Regulation of DSBR at the transcriptional level was also reported. In this study, we found that DSBR can be regulated by miR-34a at the post-transcriptional level. Specifically, miR-34a, which can be activated by DNA damages, represses DSBR activities by impairing both NHEJ and HRR pathways in cultured cells. The repression is mainly through targeting the critical DSBR promoting factor SIRT1, as ectopically expressed SIRT1 without 3＇-UTR can rescue the inhibitory roles of miR-34a on DSBR. Further studies demonstrate that SIRT1 conversely represses miR-34a expression. Taken together, our data show that miR-34a is a new repressor of DSBR and the mutual inhibition between miR-34a and SIRT1 may contribute to regulation of DNA damage repair.

关 键 词：DNA损伤修复 断裂修复 相互抑制 双链 非同源末端连接 转录后水平 蛋白相互作用 重组修复 

分 类 号：R363[医药卫生—病理学]