The yeast and human FACT chromatin-reorganizing complexes solve R-loop-mediated transcription-replication conflicts

FACT (facilitates chromatin transcription) is a chromatin-reorganizing complex that swaps nucleosomes around the RNA polymerase during transcription elongation and has a role in replication that is not fully understood yet. Here we show that recombination factors are required for the survival of yea...

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Detalhes bibliográficos
Autores: Herrera-Moyano, Emilia, Mergui, Xénia, García-Rubio, María L., Barroso, Sonia, Aguilera, Andrés
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/396476
Acesso em linha:http://hdl.handle.net/10261/396476
https://api.elsevier.com/content/abstract/scopus_id/84898841862
Access Level:acceso abierto
Palavra-chave:FACT
R loops
Chromatin reorganization
Genome instability
Transcription–replication collisions
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spelling The yeast and human FACT chromatin-reorganizing complexes solve R-loop-mediated transcription-replication conflictsHerrera-Moyano, EmiliaMergui, XéniaGarcía-Rubio, María L.Barroso, SoniaAguilera, AndrésFACTR loopsChromatin reorganizationGenome instabilityTranscription–replication collisionsFACT (facilitates chromatin transcription) is a chromatin-reorganizing complex that swaps nucleosomes around the RNA polymerase during transcription elongation and has a role in replication that is not fully understood yet. Here we show that recombination factors are required for the survival of yeast FACT mutants, consistent with an accumulation of DNA breaks that we detected by Rad52 foci and transcription-dependent hyperrecombination. Breaks also accumulate in FACT-depleted human cells, as shown by γH2AX foci and single-cell electrophoresis. Furthermore, FACT-deficient yeast and human cells show replication impairment, which in yeast we demonstrate by ChIP-chip (chromatin immunoprecipitation [ChIP] coupled with microarray analysis) of Rrm3 to occur genome-wide but preferentially at highly transcribed regions. Strikingly, in yeast FACT mutants, high levels of Rad52 foci are suppressed by RNH1 overexpression; R loops accumulate at high levels, and replication becomes normal when global RNA synthesis is inhibited in FACT-depleted human cells. The results demonstrate a key function of FACT in the resolution of R-loop-mediated transcription-replication conflicts, likely associated with a specific chromatin organization.Research was funded by grants from the Spanish Ministry of Economy and Competitiveness (Consolider CSD2007-00015 and BFU2010-16372), the Junta de Andalucı´a (CVI4567), and the European Union (FEDER). E.H.-M. was recipient of a Predoctoral Formacio´n en Investigacio ´n en Salud training grant from the Spanish Ministry of Health.Peer reviewedCold Spring Harbor Laboratory PressMinisterio de Economía y Competitividad (España)European CommissionJunta de AndalucíaMinisterio de Ciencia e Innovación (España)Ministerio de Sanidad (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252014info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/396476https://api.elsevier.com/content/abstract/scopus_id/84898841862reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MICINN//BFU2010-16372https://doi.org/10.3897/10.1101/gad.234070.113Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3964762026-05-22T06:33:51Z
dc.title.none.fl_str_mv The yeast and human FACT chromatin-reorganizing complexes solve R-loop-mediated transcription-replication conflicts
title The yeast and human FACT chromatin-reorganizing complexes solve R-loop-mediated transcription-replication conflicts
spellingShingle The yeast and human FACT chromatin-reorganizing complexes solve R-loop-mediated transcription-replication conflicts
Herrera-Moyano, Emilia
FACT
R loops
Chromatin reorganization
Genome instability
Transcription–replication collisions
title_short The yeast and human FACT chromatin-reorganizing complexes solve R-loop-mediated transcription-replication conflicts
title_full The yeast and human FACT chromatin-reorganizing complexes solve R-loop-mediated transcription-replication conflicts
title_fullStr The yeast and human FACT chromatin-reorganizing complexes solve R-loop-mediated transcription-replication conflicts
title_full_unstemmed The yeast and human FACT chromatin-reorganizing complexes solve R-loop-mediated transcription-replication conflicts
title_sort The yeast and human FACT chromatin-reorganizing complexes solve R-loop-mediated transcription-replication conflicts
dc.creator.none.fl_str_mv Herrera-Moyano, Emilia
Mergui, Xénia
García-Rubio, María L.
Barroso, Sonia
Aguilera, Andrés
author Herrera-Moyano, Emilia
author_facet Herrera-Moyano, Emilia
Mergui, Xénia
García-Rubio, María L.
Barroso, Sonia
Aguilera, Andrés
author_role author
author2 Mergui, Xénia
García-Rubio, María L.
Barroso, Sonia
Aguilera, Andrés
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
European Commission
Junta de Andalucía
Ministerio de Ciencia e Innovación (España)
Ministerio de Sanidad (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv FACT
R loops
Chromatin reorganization
Genome instability
Transcription–replication collisions
topic FACT
R loops
Chromatin reorganization
Genome instability
Transcription–replication collisions
description FACT (facilitates chromatin transcription) is a chromatin-reorganizing complex that swaps nucleosomes around the RNA polymerase during transcription elongation and has a role in replication that is not fully understood yet. Here we show that recombination factors are required for the survival of yeast FACT mutants, consistent with an accumulation of DNA breaks that we detected by Rad52 foci and transcription-dependent hyperrecombination. Breaks also accumulate in FACT-depleted human cells, as shown by γH2AX foci and single-cell electrophoresis. Furthermore, FACT-deficient yeast and human cells show replication impairment, which in yeast we demonstrate by ChIP-chip (chromatin immunoprecipitation [ChIP] coupled with microarray analysis) of Rrm3 to occur genome-wide but preferentially at highly transcribed regions. Strikingly, in yeast FACT mutants, high levels of Rad52 foci are suppressed by RNH1 overexpression; R loops accumulate at high levels, and replication becomes normal when global RNA synthesis is inhibited in FACT-depleted human cells. The results demonstrate a key function of FACT in the resolution of R-loop-mediated transcription-replication conflicts, likely associated with a specific chromatin organization.
publishDate 2014
dc.date.none.fl_str_mv 2014
2025
2025
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/10261/396476
https://api.elsevier.com/content/abstract/scopus_id/84898841862
url http://hdl.handle.net/10261/396476
https://api.elsevier.com/content/abstract/scopus_id/84898841862
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/MICINN//BFU2010-16372
https://doi.org/10.3897/10.1101/gad.234070.113
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
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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