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