Synergy between SIRT1 and SIRT6 helps recognize DNA breaks and potentiates the DNA damage response and repair in humans and mice
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 K3...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2020-06-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/55828 |
| _version_ | 1811253070426800128 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Fanbiao Meng |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T16:44:19Z |
| format | Article |
| id | doaj.art-7953ab8485c34454b0b707bc2079b45b |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:44:19Z |
| publishDate | 2020-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-7953ab8485c34454b0b707bc2079b45b2022-12-22T03:24:38ZengeLife Sciences Publications LtdeLife2050-084X2020-06-01910.7554/eLife.55828Synergy between SIRT1 and SIRT6 helps recognize DNA breaks and potentiates the DNA damage response and repair in humans and miceFanbiao Meng0https://orcid.org/0000-0002-1227-9390Minxian Qian1https://orcid.org/0000-0002-1763-2325Bin Peng2Linyuan Peng3Xiaohui Wang4Kang Zheng5https://orcid.org/0000-0002-6347-4241Zuojun Liu6Xiaolong Tang7https://orcid.org/0000-0002-4744-5846Shuju Zhang8Shimin Sun9Xinyue Cao10Qiuxiang Pang11Bosheng Zhao12Wenbin Ma13Zhou Songyang14Bo Xu15Wei-Guo Zhu16https://orcid.org/0000-0001-8385-6581Xingzhi Xu17Baohua Liu18https://orcid.org/0000-0002-1599-8059Shenzhen Key Laboratory for Systemic Aging and Intervention, National Engineering Research Center for Biotechnology (Shenzhen), Shenzhen University Health Science Center, Shenzhen, China; 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, ChinaShenzhen Key Laboratory for Systemic Aging and Intervention, National Engineering Research Center for Biotechnology (Shenzhen), Shenzhen University Health Science Center, Shenzhen, China; Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, ChinaGuangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, ChinaShenzhen Key Laboratory for Systemic Aging and Intervention, National Engineering Research Center for Biotechnology (Shenzhen), Shenzhen University Health Science Center, Shenzhen, China; Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, ChinaShenzhen Key Laboratory for Systemic Aging and Intervention, National Engineering Research Center for Biotechnology (Shenzhen), Shenzhen University Health Science Center, Shenzhen, China; International Cancer Center, Shenzhen University Health Science Center, Shenzhen, ChinaAnti-aging & Regenerative Medicine Research Institution, School of Life Sciences, Shandong University of Technology, Zibo, ChinaShenzhen Key Laboratory for Systemic Aging and Intervention, National Engineering Research Center for Biotechnology (Shenzhen), Shenzhen University Health Science Center, Shenzhen, China; Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, ChinaShenzhen Key Laboratory for Systemic Aging and Intervention, National Engineering Research Center for Biotechnology (Shenzhen), Shenzhen University Health Science Center, Shenzhen, China; Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, ChinaGuangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, ChinaShenzhen Key Laboratory for Systemic Aging and Intervention, National Engineering Research Center for Biotechnology (Shenzhen), Shenzhen University Health Science Center, Shenzhen, China; Anti-aging & Regenerative Medicine Research Institution, School of Life Sciences, Shandong University of Technology, Zibo, ChinaShenzhen Key Laboratory for Systemic Aging and Intervention, National Engineering Research Center for Biotechnology (Shenzhen), Shenzhen University Health Science Center, Shenzhen, China; Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, ChinaAnti-aging & Regenerative Medicine Research Institution, School of Life Sciences, Shandong University of Technology, Zibo, ChinaAnti-aging & Regenerative Medicine Research Institution, School of Life Sciences, Shandong University of Technology, Zibo, ChinaKey Laboratory of Gene Engineering of the Ministry of Education and State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaKey Laboratory of Gene Engineering of the Ministry of Education and State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaThe 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, ChinaGuangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, China; International Cancer Center, Shenzhen University Health Science Center, Shenzhen, ChinaGuangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, China; International Cancer Center, Shenzhen University Health Science Center, Shenzhen, ChinaShenzhen Key Laboratory for Systemic Aging and Intervention, National Engineering Research Center for Biotechnology (Shenzhen), Shenzhen University Health Science Center, Shenzhen, China; Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, China; International Cancer Center, Shenzhen University Health Science Center, Shenzhen, China; Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, ChinaThe 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.https://elifesciences.org/articles/55828SIRT1SIRT6DNA damage response (DDR)double strand DNA breaks (DSB)deacetylationγH2AX |
| spellingShingle | 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 Synergy between SIRT1 and SIRT6 helps recognize DNA breaks and potentiates the DNA damage response and repair in humans and mice eLife SIRT1 SIRT6 DNA damage response (DDR) double strand DNA breaks (DSB) deacetylation γH2AX |
| title | Synergy between SIRT1 and SIRT6 helps recognize DNA breaks and potentiates the DNA damage response and repair in humans and mice |
| title_full | Synergy between SIRT1 and SIRT6 helps recognize DNA breaks and potentiates the DNA damage response and repair in humans and mice |
| title_fullStr | Synergy between SIRT1 and SIRT6 helps recognize DNA breaks and potentiates the DNA damage response and repair in humans and mice |
| title_full_unstemmed | Synergy between SIRT1 and SIRT6 helps recognize DNA breaks and potentiates the DNA damage response and repair in humans and mice |
| title_short | Synergy between SIRT1 and SIRT6 helps recognize DNA breaks and potentiates the DNA damage response and repair in humans and mice |
| title_sort | synergy between sirt1 and sirt6 helps recognize dna breaks and potentiates the dna damage response and repair in humans and mice |
| topic | SIRT1 SIRT6 DNA damage response (DDR) double strand DNA breaks (DSB) deacetylation γH2AX |
| url | https://elifesciences.org/articles/55828 |
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