Rpd3L and Hda1 histone deacetylases facilitate repair of broken forks by promoting sister chromatid cohesion

Genome stability involves accurate replication and DNA repair. Broken replication forks, such as those encountering a nick, lead to double strand breaks (DSBs), which are preferentially repaired by sister-chromatid recombination (SCR). To decipher the role of chromatin in eukaryotic DSB repair, here...

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Detalles Bibliográficos
Autores: Ortega, Pedro, Gómez-González, Belén, Aguilera, Andrés
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/207543
Acceso en línea:http://hdl.handle.net/10261/207543
Access Level:acceso abierto
Palabra clave:DNA recombination
Genomic instability
Homologous recombination
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spelling Rpd3L and Hda1 histone deacetylases facilitate repair of broken forks by promoting sister chromatid cohesionOrtega, PedroGómez-González, BelénAguilera, AndrésDNA recombinationGenomic instabilityHomologous recombinationGenome stability involves accurate replication and DNA repair. Broken replication forks, such as those encountering a nick, lead to double strand breaks (DSBs), which are preferentially repaired by sister-chromatid recombination (SCR). To decipher the role of chromatin in eukaryotic DSB repair, here we analyze a collection of yeast chromatin-modifying mutants using a previously developed system for the molecular analysis of repair of replication-born DSBs by SCR based on a mini-HO site. We confirm the candidates through FLP-based systems based on a mutated version of the FLP flipase that causes nicks on either the leading or lagging DNA strands. We demonstrate that Rpd3L and Hda1 histone deacetylase (HDAC) complexes contribute to the repair of replication-born DSBs by facilitating cohesin loading, with no effect on other types of homology-dependent repair, thus preventing genome instability. We conclude that histone deacetylation favors general sister chromatid cohesion as a necessary step in SCR.Research was supported by the European Research Council (ERC2014 AdG669898 TARLOOP), the Spanish Ministry of Economy and Competitiveness (BFU2016-75058-P), and the European Union (FEDER). P.O. was supported by a predoctoral training grant from the Spanish Ministry of Economy and Competitiveness and B.G.-G. by the Spanish Association Against Cancer (AECC).Nature Publishing GroupEuropean Research CouncilMinisterio de Economía y Competitividad (España)European CommissionAsociación Española Contra el CáncerConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2020202020192020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/207543reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2016-75058-Phttp://dx.doi.org/10.1038/s41467-019-13210-5Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2075432026-05-22T06:33:51Z
dc.title.none.fl_str_mv Rpd3L and Hda1 histone deacetylases facilitate repair of broken forks by promoting sister chromatid cohesion
title Rpd3L and Hda1 histone deacetylases facilitate repair of broken forks by promoting sister chromatid cohesion
spellingShingle Rpd3L and Hda1 histone deacetylases facilitate repair of broken forks by promoting sister chromatid cohesion
Ortega, Pedro
DNA recombination
Genomic instability
Homologous recombination
title_short Rpd3L and Hda1 histone deacetylases facilitate repair of broken forks by promoting sister chromatid cohesion
title_full Rpd3L and Hda1 histone deacetylases facilitate repair of broken forks by promoting sister chromatid cohesion
title_fullStr Rpd3L and Hda1 histone deacetylases facilitate repair of broken forks by promoting sister chromatid cohesion
title_full_unstemmed Rpd3L and Hda1 histone deacetylases facilitate repair of broken forks by promoting sister chromatid cohesion
title_sort Rpd3L and Hda1 histone deacetylases facilitate repair of broken forks by promoting sister chromatid cohesion
dc.creator.none.fl_str_mv Ortega, Pedro
Gómez-González, Belén
Aguilera, Andrés
author Ortega, Pedro
author_facet Ortega, Pedro
Gómez-González, Belén
Aguilera, Andrés
author_role author
author2 Gómez-González, Belén
Aguilera, Andrés
author2_role author
author
dc.contributor.none.fl_str_mv European Research Council
Ministerio de Economía y Competitividad (España)
European Commission
Asociación Española Contra el Cáncer
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv DNA recombination
Genomic instability
Homologous recombination
topic DNA recombination
Genomic instability
Homologous recombination
description Genome stability involves accurate replication and DNA repair. Broken replication forks, such as those encountering a nick, lead to double strand breaks (DSBs), which are preferentially repaired by sister-chromatid recombination (SCR). To decipher the role of chromatin in eukaryotic DSB repair, here we analyze a collection of yeast chromatin-modifying mutants using a previously developed system for the molecular analysis of repair of replication-born DSBs by SCR based on a mini-HO site. We confirm the candidates through FLP-based systems based on a mutated version of the FLP flipase that causes nicks on either the leading or lagging DNA strands. We demonstrate that Rpd3L and Hda1 histone deacetylase (HDAC) complexes contribute to the repair of replication-born DSBs by facilitating cohesin loading, with no effect on other types of homology-dependent repair, thus preventing genome instability. We conclude that histone deacetylation favors general sister chromatid cohesion as a necessary step in SCR.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/207543
url http://hdl.handle.net/10261/207543
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2016-75058-P
http://dx.doi.org/10.1038/s41467-019-13210-5
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
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