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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
Shenzhen University;
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Minxian Qian
Shenzhen University;
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Bin Peng
Shenzhen University;
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Xiaohui Wang
Shenzhen University;
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Linyuan Peng
Shenzhen University;
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Kang Zheng
Shandong University of Technology;
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Zuojun Liu
Shenzhen University;
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Xiaolong Tang
Shenzhen University;
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Shuju Zhang
Shenzhen University;
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Shimin Sun
Shenzhen University;
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Xinyue Cao
Shenzhen University;
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Qiuxiang Pang
Shandong University of Technology;
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Bosheng Zhao
Shandong University of Technology;
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Wenbin Ma
Sun Yat-sen University;
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Zhou Songyang
Sun Yat-sen University;
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Bo Xu
Tianjin Medical University;
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Wei-Guo Zhu
Shenzhen University;
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Xingzhi Xu
Shenzhen University;
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Baohua Liu
Shenzhen University Health Science Center
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  • For correspondence: ppliew@szu.edu.cn
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Abstract

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.

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Posted February 02, 2020.
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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
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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

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