The yeast and human FACT chromatin-reorganizing complexes resolve 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, Xenia, García Rubio, María Luisa, Barroso Ceballos, Sonia Inés, Aguilera López, Andrés
Formato: artículo
Fecha de publicación:2014
País:España
Recursos:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/29091
Acesso em linha:http://hdl.handle.net/11441/29091
https://doi.org/10.1101/gad.234070.113
Access Level:acceso abierto
Palavra-chave:FACT
transcription–replication collisions
R loops
genome instability
chromatin reorganization
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spelling The yeast and human FACT chromatin-reorganizing complexes resolve R-loop-mediated transcription-replication conflictsHerrera Moyano, EmiliaMergui, XeniaGarcía Rubio, María LuisaBarroso Ceballos, Sonia InésAguilera López, AndrésFACTtranscription–replication collisionsR loopsgenome instabilitychromatin reorganizationFACT (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.Cold Spring Harbor Laboratory PressGenética2014info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttp://hdl.handle.net/11441/29091https://doi.org/10.1101/gad.234070.113reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésGenes & development, 28(7), 735-748http://dx.doi.org/10.1101/gad.234070.113info:eu-repo/semantics/openAccessoai:idus.us.es:11441/290912026-06-17T12:51:07Z
dc.title.none.fl_str_mv The yeast and human FACT chromatin-reorganizing complexes resolve R-loop-mediated transcription-replication conflicts
title The yeast and human FACT chromatin-reorganizing complexes resolve R-loop-mediated transcription-replication conflicts
spellingShingle The yeast and human FACT chromatin-reorganizing complexes resolve R-loop-mediated transcription-replication conflicts
Herrera Moyano, Emilia
FACT
transcription–replication collisions
R loops
genome instability
chromatin reorganization
title_short The yeast and human FACT chromatin-reorganizing complexes resolve R-loop-mediated transcription-replication conflicts
title_full The yeast and human FACT chromatin-reorganizing complexes resolve R-loop-mediated transcription-replication conflicts
title_fullStr The yeast and human FACT chromatin-reorganizing complexes resolve R-loop-mediated transcription-replication conflicts
title_full_unstemmed The yeast and human FACT chromatin-reorganizing complexes resolve R-loop-mediated transcription-replication conflicts
title_sort The yeast and human FACT chromatin-reorganizing complexes resolve R-loop-mediated transcription-replication conflicts
dc.creator.none.fl_str_mv Herrera Moyano, Emilia
Mergui, Xenia
García Rubio, María Luisa
Barroso Ceballos, Sonia Inés
Aguilera López, Andrés
author Herrera Moyano, Emilia
author_facet Herrera Moyano, Emilia
Mergui, Xenia
García Rubio, María Luisa
Barroso Ceballos, Sonia Inés
Aguilera López, Andrés
author_role author
author2 Mergui, Xenia
García Rubio, María Luisa
Barroso Ceballos, Sonia Inés
Aguilera López, Andrés
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Genética
dc.subject.none.fl_str_mv FACT
transcription–replication collisions
R loops
genome instability
chromatin reorganization
topic FACT
transcription–replication collisions
R loops
genome instability
chromatin reorganization
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
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/11441/29091
https://doi.org/10.1101/gad.234070.113
url http://hdl.handle.net/11441/29091
https://doi.org/10.1101/gad.234070.113
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Genes & development, 28(7), 735-748
http://dx.doi.org/10.1101/gad.234070.113
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
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:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301629

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