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Synergy between SIRT1 and SIRT6 helps recognize DNA breaks and potentiates the DNA damage response and repair in humans and mice

Authors :
Fanbiao Meng
Minxian Qian
Bin Peng
Linyuan Peng
Xiaohui Wang
Kang Zheng
Zuojun Liu
Xiaolong Tang
Shuju Zhang
Shimin Sun
Xinyue Cao
Qiuxiang Pang
Bosheng Zhao
Wenbin Ma
Zhou Songyang
Bo Xu
Wei-Guo Zhu
Xingzhi Xu
Baohua Liu
Source :
eLife, Vol 9 (2020)
Publication Year :
2020
Publisher :
eLife Sciences Publications Ltd, 2020.

Abstract

The DNA damage response (DDR) is a highly orchestrated process but how double-strand DNA breaks (DSBs) are initially recognized is unclear. Here, we show that polymerized SIRT6 deacetylase recognizes DSBs and potentiates the DDR in human and mouse cells. First, SIRT1 deacetylates SIRT6 at residue K33, which is important for SIRT6 polymerization and mobilization toward DSBs. Then, K33-deacetylated SIRT6 anchors to γH2AX, allowing its retention on and subsequent remodeling of local chromatin. We show that a K33R mutation that mimics hypoacetylated SIRT6 can rescue defective DNA repair as a result of SIRT1 deficiency in cultured cells. These data highlight the synergistic action between SIRTs in the spatiotemporal regulation of the DDR and DNA repair in humans and mice.

Details

Language :
English
ISSN :
2050084X
Volume :
9
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.7953ab8485c34454b0b707bc2079b45b
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.55828