The SWR1 Histone Replacement Complex Causes Genetic Instability and Genome-Wide Transcription Misregulation in the Absence of H2A.Z

13 páginas, 6 figuras.

Detalles Bibliográficos
Autores: Morillo-Huesca, Macarena, Clemente-Ruiz, Marta, Andújar, Eloísa, Prado, Félix
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2010
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/42430
Acceso en línea:http://hdl.handle.net/10261/42430
Access Level:acceso abierto
Palabra clave:Adenosine triphosphatases
Chromatin
Genome
Genomic instability
Histones
Saccharomyces cerevisiae
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spelling The SWR1 Histone Replacement Complex Causes Genetic Instability and Genome-Wide Transcription Misregulation in the Absence of H2A.ZMorillo-Huesca, MacarenaClemente-Ruiz, MartaAndújar, EloísaPrado, FélixAdenosine triphosphatasesChromatinGenomeGenomic instabilityHistonesSaccharomyces cerevisiae13 páginas, 6 figuras.This is an open-access article distributed under the terms of the Creative Commons Attribution License.The SWR1 complex replaces the canonical histone H2A with the variant H2A.Z (Htz1 in yeast) at specific chromatin regions. This dynamic alteration in nucleosome structure provides a molecular mechanism to regulate transcription, gene silencing, chromosome segregation and DNA repair. Here we show that genetic instability, sensitivity to drugs impairing different cellular processes and genome-wide transcriptional misregulation in htz1Δ can be partially or totally suppressed if SWR1 is not formed (swr1Δ), if it forms but cannot bind to chromatin (swc2Δ) or if it binds to chromatin but lacks histone replacement activity (swc5Δ and the ATPase-dead swr1-K727G). These results suggest that in htz1Δ the nucleosome remodelling activity of SWR1 affects chromatin integrity because of an attempt to replace H2A with Htz1 in the absence of the latter. This would impair transcription and, either directly or indirectly, other cellular processes. Specifically, we show that in htz1Δ, the SWR1 complex causes an accumulation of recombinogenic DNA damage by a mechanism dependent on phosphorylation of H2A at Ser129, a modification that occurs in response to DNA damage, suggesting that the SWR1 complex impairs the repair of spontaneous DNA damage in htz1Δ. In addition, SWR1 causes DSBs sensitivity in htz1Δ; consistently, in the absence of Htz1 the SWR1 complex bound near an endonuclease HO-induced DSB at the mating-type (MAT) locus impairs DSB-induced checkpoint activation. Our results support a stepwise mechanism for the replacement of H2A with Htz1 and demonstrate that a tight control of this mechanism is essential to regulate chromatin dynamics but also to prevent the deleterious consequences of an incomplete nucleosome remodelling.The research was funded by the Spanish Ministry of Education and Science (BFU2006-08336 grant) and the Junta de Andalucia (P07-CVI-032000). M.C-R. was a recipient of a pre-doctoral training grant from the Spanish Research Council (CSIC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublic Library of ScienceMinisterio de Educación y Ciencia (España)Junta de AndalucíaConsejo Superior de Investigaciones Científicas (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201120112010info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/42430reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1371/journal.pone.0012143Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/424302026-05-22T06:33:51Z
dc.title.none.fl_str_mv The SWR1 Histone Replacement Complex Causes Genetic Instability and Genome-Wide Transcription Misregulation in the Absence of H2A.Z
title The SWR1 Histone Replacement Complex Causes Genetic Instability and Genome-Wide Transcription Misregulation in the Absence of H2A.Z
spellingShingle The SWR1 Histone Replacement Complex Causes Genetic Instability and Genome-Wide Transcription Misregulation in the Absence of H2A.Z
Morillo-Huesca, Macarena
Adenosine triphosphatases
Chromatin
Genome
Genomic instability
Histones
Saccharomyces cerevisiae
title_short The SWR1 Histone Replacement Complex Causes Genetic Instability and Genome-Wide Transcription Misregulation in the Absence of H2A.Z
title_full The SWR1 Histone Replacement Complex Causes Genetic Instability and Genome-Wide Transcription Misregulation in the Absence of H2A.Z
title_fullStr The SWR1 Histone Replacement Complex Causes Genetic Instability and Genome-Wide Transcription Misregulation in the Absence of H2A.Z
title_full_unstemmed The SWR1 Histone Replacement Complex Causes Genetic Instability and Genome-Wide Transcription Misregulation in the Absence of H2A.Z
title_sort The SWR1 Histone Replacement Complex Causes Genetic Instability and Genome-Wide Transcription Misregulation in the Absence of H2A.Z
dc.creator.none.fl_str_mv Morillo-Huesca, Macarena
Clemente-Ruiz, Marta
Andújar, Eloísa
Prado, Félix
author Morillo-Huesca, Macarena
author_facet Morillo-Huesca, Macarena
Clemente-Ruiz, Marta
Andújar, Eloísa
Prado, Félix
author_role author
author2 Clemente-Ruiz, Marta
Andújar, Eloísa
Prado, Félix
author2_role author
author
author
dc.contributor.none.fl_str_mv Ministerio de Educación y Ciencia (España)
Junta de Andalucía
Consejo Superior de Investigaciones Científicas (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Adenosine triphosphatases
Chromatin
Genome
Genomic instability
Histones
Saccharomyces cerevisiae
topic Adenosine triphosphatases
Chromatin
Genome
Genomic instability
Histones
Saccharomyces cerevisiae
description 13 páginas, 6 figuras.
publishDate 2010
dc.date.none.fl_str_mv 2010
2011
2011
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/10261/42430
url http://hdl.handle.net/10261/42430
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1371/journal.pone.0012143
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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
repository.mail.fl_str_mv
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score 15,812429

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