2. Academic Validation
  3. Synergy between SIRT1 and SIRT6 helps recognize DNA breaks and potentiates the DNA damage response and repair in humans and mice

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

  • Elife. 2020 Jun 15;9:e55828. doi: 10.7554/eLife.55828.
Fanbiao Meng # 1 2,  Minxian Qian # 1 3,  Bin Peng # 3,  Linyuan Peng 1 3,  Xiaohui Wang 1 4,  Kang Zheng 5,  Zuojun Liu 1 3,  Xiaolong Tang 1 3,  Shuju Zhang 3,  Shimin Sun 1 5,  Xinyue Cao 1 3,  Qiuxiang Pang 5,  Bosheng Zhao 5,  Wenbin Ma 6,  Zhou Songyang 6,  Bo Xu 2,  Wei-Guo Zhu 3 4,  Xingzhi Xu 3 4,  Baohua Liu 1 3 4 7
Affiliations

Affiliations

  • 1 Shenzhen Key Laboratory for Systemic Aging and Intervention, National Engineering Research Center for Biotechnology (Shenzhen), Shenzhen University Health Science Center, Shenzhen, China.
  • 2 The Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
  • 3 Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, China.
  • 4 International Cancer Center, Shenzhen University Health Science Center, Shenzhen, China.
  • 5 Anti-aging & Regenerative Medicine Research Institution, School of Life Sciences, Shandong University of Technology, Zibo, China.
  • 6 Key Laboratory of Gene Engineering of the Ministry of Education and State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • 7 Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, China.
  • # Contributed equally.
PMID: 32538779 DOI: 10.7554/eLife.55828
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.

Keywords

DNA damage response (DDR); SIRT1; SIRT6; biochemistry; chemical biology; deacetylation; double strand DNA breaks (DSB); human; mouse; γH2AX.

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