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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
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...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324161/ https://www.ncbi.nlm.nih.gov/pubmed/32538779 http://dx.doi.org/10.7554/eLife.55828 |
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author | Meng, Fanbiao Qian, Minxian Peng, Bin Peng, Linyuan Wang, Xiaohui Zheng, Kang Liu, Zuojun Tang, Xiaolong Zhang, Shuju Sun, Shimin Cao, Xinyue Pang, Qiuxiang Zhao, Bosheng Ma, Wenbin Songyang, Zhou Xu, Bo Zhu, Wei-Guo Xu, Xingzhi Liu, Baohua |
author_facet | Meng, Fanbiao Qian, Minxian Peng, Bin Peng, Linyuan Wang, Xiaohui Zheng, Kang Liu, Zuojun Tang, Xiaolong Zhang, Shuju Sun, Shimin Cao, Xinyue Pang, Qiuxiang Zhao, Bosheng Ma, Wenbin Songyang, Zhou Xu, Bo Zhu, Wei-Guo Xu, Xingzhi Liu, Baohua |
author_sort | Meng, Fanbiao |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-7324161 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-73241612020-07-01 Synergy between SIRT1 and SIRT6 helps recognize DNA breaks and potentiates the DNA damage response and repair in humans and mice Meng, Fanbiao Qian, Minxian Peng, Bin Peng, Linyuan Wang, Xiaohui Zheng, Kang Liu, Zuojun Tang, Xiaolong Zhang, Shuju Sun, Shimin Cao, Xinyue Pang, Qiuxiang Zhao, Bosheng Ma, Wenbin Songyang, Zhou Xu, Bo Zhu, Wei-Guo Xu, Xingzhi Liu, Baohua eLife Biochemistry and Chemical Biology 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. eLife Sciences Publications, Ltd 2020-06-15 /pmc/articles/PMC7324161/ /pubmed/32538779 http://dx.doi.org/10.7554/eLife.55828 Text en © 2020, Meng et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biochemistry and Chemical Biology Meng, Fanbiao Qian, Minxian Peng, Bin Peng, Linyuan Wang, Xiaohui Zheng, Kang Liu, Zuojun Tang, Xiaolong Zhang, Shuju Sun, Shimin Cao, Xinyue Pang, Qiuxiang Zhao, Bosheng Ma, Wenbin Songyang, Zhou Xu, Bo Zhu, Wei-Guo Xu, Xingzhi Liu, Baohua Synergy between SIRT1 and SIRT6 helps recognize DNA breaks and potentiates the DNA damage response and repair in humans and mice |
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 | Biochemistry and Chemical Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324161/ https://www.ncbi.nlm.nih.gov/pubmed/32538779 http://dx.doi.org/10.7554/eLife.55828 |
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