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A PARP1–BRG1–SIRT1 axis promotes HR repair by reducing nucleosome density at DNA damage sites
Creating access to DNA double-strand break (DSB) sites in the chromatin context is an essential step during the repair process, but much remains to be determined about its regulatory mechanisms. Here, using a novel reporter cassette for simultaneous detection of homologous recombination (HR) and non...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145522/ https://www.ncbi.nlm.nih.gov/pubmed/31291457 http://dx.doi.org/10.1093/nar/gkz592 |
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author | Chen, Yu Zhang, Haiping Xu, Zhu Tang, Huanyin Geng, Anke Cai, Bailian Su, Tao Shi, Jiejun Jiang, Cizhong Tian, Xiao Seluanov, Andrei Huang, Jun Wan, Xiaoping Jiang, Ying Gorbunova, Vera Mao, Zhiyong |
author_facet | Chen, Yu Zhang, Haiping Xu, Zhu Tang, Huanyin Geng, Anke Cai, Bailian Su, Tao Shi, Jiejun Jiang, Cizhong Tian, Xiao Seluanov, Andrei Huang, Jun Wan, Xiaoping Jiang, Ying Gorbunova, Vera Mao, Zhiyong |
author_sort | Chen, Yu |
collection | PubMed |
description | Creating access to DNA double-strand break (DSB) sites in the chromatin context is an essential step during the repair process, but much remains to be determined about its regulatory mechanisms. Here, using a novel reporter cassette for simultaneous detection of homologous recombination (HR) and nonhomologous end joining (NHEJ) at the same chromosomal site, we report that the efficiency of HR but not NHEJ negatively correlates with nucleosome density. We demonstrate that PARP1 is required for HR by modulating nucleosome density at damage sites. Mechanistic studies indicate that the ATPase domain of BRG1 and the ZnF domain of SIRT1 interact with poly-ADP ribose (PAR) in response to DNA damage, and are responsible for bringing the two factors to broken DNA ends. At DNA damage sites, BRG1 and SIRT1 physically interact, whereupon SIRT1 deacetylates BRG1 at lysine residues 1029 and 1033, stimulating its ATPase activity to remodel chromatin and promote HR. |
format | Online Article Text |
id | pubmed-7145522 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-71455222020-04-13 A PARP1–BRG1–SIRT1 axis promotes HR repair by reducing nucleosome density at DNA damage sites Chen, Yu Zhang, Haiping Xu, Zhu Tang, Huanyin Geng, Anke Cai, Bailian Su, Tao Shi, Jiejun Jiang, Cizhong Tian, Xiao Seluanov, Andrei Huang, Jun Wan, Xiaoping Jiang, Ying Gorbunova, Vera Mao, Zhiyong Nucleic Acids Res Genome Integrity, Repair and Replication Creating access to DNA double-strand break (DSB) sites in the chromatin context is an essential step during the repair process, but much remains to be determined about its regulatory mechanisms. Here, using a novel reporter cassette for simultaneous detection of homologous recombination (HR) and nonhomologous end joining (NHEJ) at the same chromosomal site, we report that the efficiency of HR but not NHEJ negatively correlates with nucleosome density. We demonstrate that PARP1 is required for HR by modulating nucleosome density at damage sites. Mechanistic studies indicate that the ATPase domain of BRG1 and the ZnF domain of SIRT1 interact with poly-ADP ribose (PAR) in response to DNA damage, and are responsible for bringing the two factors to broken DNA ends. At DNA damage sites, BRG1 and SIRT1 physically interact, whereupon SIRT1 deacetylates BRG1 at lysine residues 1029 and 1033, stimulating its ATPase activity to remodel chromatin and promote HR. Oxford University Press 2019-09-19 2019-07-10 /pmc/articles/PMC7145522/ /pubmed/31291457 http://dx.doi.org/10.1093/nar/gkz592 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Genome Integrity, Repair and Replication Chen, Yu Zhang, Haiping Xu, Zhu Tang, Huanyin Geng, Anke Cai, Bailian Su, Tao Shi, Jiejun Jiang, Cizhong Tian, Xiao Seluanov, Andrei Huang, Jun Wan, Xiaoping Jiang, Ying Gorbunova, Vera Mao, Zhiyong A PARP1–BRG1–SIRT1 axis promotes HR repair by reducing nucleosome density at DNA damage sites |
title | A PARP1–BRG1–SIRT1 axis promotes HR repair by reducing nucleosome density at DNA damage sites |
title_full | A PARP1–BRG1–SIRT1 axis promotes HR repair by reducing nucleosome density at DNA damage sites |
title_fullStr | A PARP1–BRG1–SIRT1 axis promotes HR repair by reducing nucleosome density at DNA damage sites |
title_full_unstemmed | A PARP1–BRG1–SIRT1 axis promotes HR repair by reducing nucleosome density at DNA damage sites |
title_short | A PARP1–BRG1–SIRT1 axis promotes HR repair by reducing nucleosome density at DNA damage sites |
title_sort | parp1–brg1–sirt1 axis promotes hr repair by reducing nucleosome density at dna damage sites |
topic | Genome Integrity, Repair and Replication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145522/ https://www.ncbi.nlm.nih.gov/pubmed/31291457 http://dx.doi.org/10.1093/nar/gkz592 |
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