New Results
A synergistic action of sirtuins directly recognizes DNA breaks and potentiates DNA damage response and repair
Fanbiao Meng, Minxian Qian, Bin Peng, Xiaohui Wang, Linyuan Peng, 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
doi: https://doi.org/10.1101/2020.02.01.930172
Fanbiao Meng
1Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518055, China
2The 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 300006, China
Minxian Qian
1Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518055, China
3Shenzhen Key Laboratory for Systemic Aging and Intervention, National Engineering Research Center for Biotechnology (Shenzhen), Shenzhen University Health Science Center, Shenzhen 518055, China
5Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518060, China
Bin Peng
1Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518055, China
Xiaohui Wang
1Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518055, China
6Carson International Cancer Center, Shenzhen University Health Science Center, Shenzhen 518055, China
Linyuan Peng
1Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518055, China
3Shenzhen Key Laboratory for Systemic Aging and Intervention, National Engineering Research Center for Biotechnology (Shenzhen), Shenzhen University Health Science Center, Shenzhen 518055, China
5Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518060, China
Kang Zheng
7Anti-aging & Regenerative Medicine Research Institution, School of Life Sciences, Shandong University of Technology, Zibo 255049, China
Zuojun Liu
1Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518055, China
3Shenzhen Key Laboratory for Systemic Aging and Intervention, National Engineering Research Center for Biotechnology (Shenzhen), Shenzhen University Health Science Center, Shenzhen 518055, China
5Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518060, China
Xiaolong Tang
1Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518055, China
3Shenzhen Key Laboratory for Systemic Aging and Intervention, National Engineering Research Center for Biotechnology (Shenzhen), Shenzhen University Health Science Center, Shenzhen 518055, China
5Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518060, China
Shuju Zhang
1Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518055, China
Shimin Sun
1Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518055, China
7Anti-aging & Regenerative Medicine Research Institution, School of Life Sciences, Shandong University of Technology, Zibo 255049, China
Xinyue Cao
1Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518055, China
3Shenzhen Key Laboratory for Systemic Aging and Intervention, National Engineering Research Center for Biotechnology (Shenzhen), Shenzhen University Health Science Center, Shenzhen 518055, China
5Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518060, China
Qiuxiang Pang
7Anti-aging & Regenerative Medicine Research Institution, School of Life Sciences, Shandong University of Technology, Zibo 255049, China
Bosheng Zhao
7Anti-aging & Regenerative Medicine Research Institution, School of Life Sciences, Shandong University of Technology, Zibo 255049, China
Wenbin Ma
8Key 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
Zhou Songyang
8Key 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
Bo Xu
2The 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 300006, China
Wei-Guo Zhu
1Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518055, China
5Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518060, China
6Carson International Cancer Center, Shenzhen University Health Science Center, Shenzhen 518055, China
Xingzhi Xu
1Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518055, China
6Carson International Cancer Center, Shenzhen University Health Science Center, Shenzhen 518055, China
Baohua Liu
1Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518055, China
3Shenzhen Key Laboratory for Systemic Aging and Intervention, National Engineering Research Center for Biotechnology (Shenzhen), Shenzhen University Health Science Center, Shenzhen 518055, China
4Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen 518055, China
5Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518060, China
6Carson International Cancer Center, Shenzhen University Health Science Center, Shenzhen 518055, China
Summary
DNA damage response (DDR) is a highly orchestrated process; initially how the DNA breaks are recognized need in-depth study. Here, we show that polymerized SIRT6 deacetylase recognizes double-strand DNA breaks (DSBs) and potentiates DDR. SIRT1 deacetylates SIRT6 at residue K33, which is important for SIRT6 polymerization and mobilization toward DNA breaks. The K33-deacetylated SIRT6 anchors to γH2AX, allowing its retention on and subsequent remodeling of local chromatin. The K33R mutation, mimicking hypoacetylated SIRT6, rescues defective DNA repair imposed by SIRT1 deficiency in cells. Our data highlights a synergistic action of SIRTs in spatiotemporal regulation of DDR and DNA repair.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Posted February 02, 2020.
A synergistic action of sirtuins directly recognizes DNA breaks and potentiates DNA damage response and repair
Fanbiao Meng, Minxian Qian, Bin Peng, Xiaohui Wang, Linyuan Peng, 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
bioRxiv 2020.02.01.930172; doi: https://doi.org/10.1101/2020.02.01.930172
A synergistic action of sirtuins directly recognizes DNA breaks and potentiates DNA damage response and repair
Fanbiao Meng, Minxian Qian, Bin Peng, Xiaohui Wang, Linyuan Peng, 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
bioRxiv 2020.02.01.930172; doi: https://doi.org/10.1101/2020.02.01.930172
Subject Area
Subject Areas
- Biochemistry (11561)
- Bioengineering (8622)
- Bioinformatics (28861)
- Biophysics (14793)
- Cancer Biology (11918)
- Cell Biology (17159)
- Clinical Trials (138)
- Developmental Biology (9302)
- Ecology (14019)
- Epidemiology (2067)
- Evolutionary Biology (18128)
- Genetics (12144)
- Genomics (16615)
- Immunology (11706)
- Microbiology (27689)
- Molecular Biology (11384)
- Neuroscience (60089)
- Paleontology (447)
- Pathology (1847)
- Pharmacology and Toxicology (3183)
- Physiology (4878)
- Plant Biology (10276)
- Synthetic Biology (2849)
- Systems Biology (7289)
- Zoology (1618)