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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
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.
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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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