Differential contribution of HP1 proteins to DNA end resection and homology-directed repair

Autores
Soria, Ramiro Gaston; Almouzni, Geneviéve
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Heterochromatin protein 1 paralogs (HP1α, β and γ in mammals) are not only central in heterochromatin organization, but have also been linked to transcriptional activation at euchromatic regions, maintenance of telomere stability and, most recently, to the DNA damage response (DDR). However, how HP1 proteins contribute to the DDR at a molecular level, and whether HP1 paralogs within the same organism, as well as their respective orthologs, have overlapping or unique roles in the DDR, remain to be elucidated. Herein, we have combined the analysis of the efficiency and kinetics of recruitment of key repair proteins to sites of DNA damage with specific DNA repair assays to demonstrate that human HP1 paralogs differentially modulate homology-directed repair (HDR) pathways, including homologous recombination (HR) and single-strand annealing (SSA). We find that while HP1α and β stimulate HR and SSA, HP1γ has an inhibitory role. In addition, we show that the stimulatory role of HP1α and β in HDR is linked to the DNA-end resection step of DNA breaks, through the promotion of RPA loading and phosphorylation at damage sites. Altogether, our findings provide mechanistic insight into how human HP1 proteins participate in the recombination process, emerging as important chromatin regulators during HDR.
Fil: Soria, Ramiro Gaston. Centre National de la Recherche Scientifique; Francia. Institut Curie Section Recherche; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Almouzni, Geneviéve. Centre National de la Recherche Scientifique; Francia. Institut Curie Section Recherche; Francia
Materia
Heterochromatin
Dna Repair
Dna Damage Response
Homologous Recombination
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/7557

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spelling Differential contribution of HP1 proteins to DNA end resection and homology-directed repairSoria, Ramiro GastonAlmouzni, GeneviéveHeterochromatinDna RepairDna Damage ResponseHomologous Recombinationhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Heterochromatin protein 1 paralogs (HP1α, β and γ in mammals) are not only central in heterochromatin organization, but have also been linked to transcriptional activation at euchromatic regions, maintenance of telomere stability and, most recently, to the DNA damage response (DDR). However, how HP1 proteins contribute to the DDR at a molecular level, and whether HP1 paralogs within the same organism, as well as their respective orthologs, have overlapping or unique roles in the DDR, remain to be elucidated. Herein, we have combined the analysis of the efficiency and kinetics of recruitment of key repair proteins to sites of DNA damage with specific DNA repair assays to demonstrate that human HP1 paralogs differentially modulate homology-directed repair (HDR) pathways, including homologous recombination (HR) and single-strand annealing (SSA). We find that while HP1α and β stimulate HR and SSA, HP1γ has an inhibitory role. In addition, we show that the stimulatory role of HP1α and β in HDR is linked to the DNA-end resection step of DNA breaks, through the promotion of RPA loading and phosphorylation at damage sites. Altogether, our findings provide mechanistic insight into how human HP1 proteins participate in the recombination process, emerging as important chromatin regulators during HDR.Fil: Soria, Ramiro Gaston. Centre National de la Recherche Scientifique; Francia. Institut Curie Section Recherche; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Almouzni, Geneviéve. Centre National de la Recherche Scientifique; Francia. Institut Curie Section Recherche; FranciaTaylor & Francis2013-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/7557Soria, Ramiro Gaston; Almouzni, Geneviéve; Differential contribution of HP1 proteins to DNA end resection and homology-directed repair; Taylor & Francis; Cell Cycle; 12; 2-2013; 422-4291538-4101enginfo:eu-repo/semantics/altIdentifier/url/http://www.tandfonline.com/doi/full/10.4161/cc.23215info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587443/info:eu-repo/semantics/altIdentifier/doi/10.4161/cc.23215info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:15:38Zoai:ri.conicet.gov.ar:11336/7557instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:15:38.717CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Differential contribution of HP1 proteins to DNA end resection and homology-directed repair
title Differential contribution of HP1 proteins to DNA end resection and homology-directed repair
spellingShingle Differential contribution of HP1 proteins to DNA end resection and homology-directed repair
Soria, Ramiro Gaston
Heterochromatin
Dna Repair
Dna Damage Response
Homologous Recombination
title_short Differential contribution of HP1 proteins to DNA end resection and homology-directed repair
title_full Differential contribution of HP1 proteins to DNA end resection and homology-directed repair
title_fullStr Differential contribution of HP1 proteins to DNA end resection and homology-directed repair
title_full_unstemmed Differential contribution of HP1 proteins to DNA end resection and homology-directed repair
title_sort Differential contribution of HP1 proteins to DNA end resection and homology-directed repair
dc.creator.none.fl_str_mv Soria, Ramiro Gaston
Almouzni, Geneviéve
author Soria, Ramiro Gaston
author_facet Soria, Ramiro Gaston
Almouzni, Geneviéve
author_role author
author2 Almouzni, Geneviéve
author2_role author
dc.subject.none.fl_str_mv Heterochromatin
Dna Repair
Dna Damage Response
Homologous Recombination
topic Heterochromatin
Dna Repair
Dna Damage Response
Homologous Recombination
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Heterochromatin protein 1 paralogs (HP1α, β and γ in mammals) are not only central in heterochromatin organization, but have also been linked to transcriptional activation at euchromatic regions, maintenance of telomere stability and, most recently, to the DNA damage response (DDR). However, how HP1 proteins contribute to the DDR at a molecular level, and whether HP1 paralogs within the same organism, as well as their respective orthologs, have overlapping or unique roles in the DDR, remain to be elucidated. Herein, we have combined the analysis of the efficiency and kinetics of recruitment of key repair proteins to sites of DNA damage with specific DNA repair assays to demonstrate that human HP1 paralogs differentially modulate homology-directed repair (HDR) pathways, including homologous recombination (HR) and single-strand annealing (SSA). We find that while HP1α and β stimulate HR and SSA, HP1γ has an inhibitory role. In addition, we show that the stimulatory role of HP1α and β in HDR is linked to the DNA-end resection step of DNA breaks, through the promotion of RPA loading and phosphorylation at damage sites. Altogether, our findings provide mechanistic insight into how human HP1 proteins participate in the recombination process, emerging as important chromatin regulators during HDR.
Fil: Soria, Ramiro Gaston. Centre National de la Recherche Scientifique; Francia. Institut Curie Section Recherche; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Almouzni, Geneviéve. Centre National de la Recherche Scientifique; Francia. Institut Curie Section Recherche; Francia
description Heterochromatin protein 1 paralogs (HP1α, β and γ in mammals) are not only central in heterochromatin organization, but have also been linked to transcriptional activation at euchromatic regions, maintenance of telomere stability and, most recently, to the DNA damage response (DDR). However, how HP1 proteins contribute to the DDR at a molecular level, and whether HP1 paralogs within the same organism, as well as their respective orthologs, have overlapping or unique roles in the DDR, remain to be elucidated. Herein, we have combined the analysis of the efficiency and kinetics of recruitment of key repair proteins to sites of DNA damage with specific DNA repair assays to demonstrate that human HP1 paralogs differentially modulate homology-directed repair (HDR) pathways, including homologous recombination (HR) and single-strand annealing (SSA). We find that while HP1α and β stimulate HR and SSA, HP1γ has an inhibitory role. In addition, we show that the stimulatory role of HP1α and β in HDR is linked to the DNA-end resection step of DNA breaks, through the promotion of RPA loading and phosphorylation at damage sites. Altogether, our findings provide mechanistic insight into how human HP1 proteins participate in the recombination process, emerging as important chromatin regulators during HDR.
publishDate 2013
dc.date.none.fl_str_mv 2013-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/7557
Soria, Ramiro Gaston; Almouzni, Geneviéve; Differential contribution of HP1 proteins to DNA end resection and homology-directed repair; Taylor & Francis; Cell Cycle; 12; 2-2013; 422-429
1538-4101
url http://hdl.handle.net/11336/7557
identifier_str_mv Soria, Ramiro Gaston; Almouzni, Geneviéve; Differential contribution of HP1 proteins to DNA end resection and homology-directed repair; Taylor & Francis; Cell Cycle; 12; 2-2013; 422-429
1538-4101
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.tandfonline.com/doi/full/10.4161/cc.23215
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587443/
info:eu-repo/semantics/altIdentifier/doi/10.4161/cc.23215
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Taylor & Francis
publisher.none.fl_str_mv Taylor & Francis
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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