SIRT6 recruits SNF2H to sites of DNA breaks, preventing genomic instability through chromatin remodeling

Autores
Toiber, Deborah; Erdel, Fabian; Bouazoune, Karim; Silberman, Dafne Magali; Zhong, Lei; Mulligan, Peter; Sebastián, Carlos; Cosentino, Claudia; Martínez Pastor, Bárbara; Giacosa, Sofia; D´Urso, Agustina; Näär, Anders M.; Kingston, Robert; Rippe, Karsten; Mostoslavsky, Raul
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
DNA damage is linked to multiple human diseases, such as cancer, neurodegeneration, and aging. Little is known about the role of chromatin accessibility in DNA repair. Here, we find that the deacetylase sirtuin 6 (SIRT6) is one of the earliest factors recruited to double-strand breaks (DSBs). SIRT6 recruits the chromatin remodeler SNF2H to DSBs and focally deacetylates histone H3K56. Lack of SIRT6 and SNF2H impairs chromatin remodeling, increasing sensitivity to genotoxic damage and recruitment of downstream factors such as 53BP1 and breast cancer 1 (BRCA1). Remarkably, SIRT6-deficient mice exhibit lower levels of chromatin-associated SNF2H in specific tissues, a phenotype accompanied by DNA damage. We demonstrate that SIRT6 is critical for recruitment of a chromatin remodeler as an early step in the DNA damage response, indicating that proper unfolding of chromatin plays a rate-limiting role. We present a unique crosstalk between a histone modifier and a chromatin remodeler, regulating a coordinated response to prevent DNA damage.
Fil: Toiber, Deborah. Harvard Medical School; Estados Unidos
Fil: Erdel, Fabian. Deutsches Krebsforschungszentrum; Alemania
Fil: Bouazoune, Karim. Harvard Medical School; Estados Unidos
Fil: Silberman, Dafne Magali. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Harvard Medical School; Estados Unidos
Fil: Zhong, Lei. Harvard Medical School; Estados Unidos
Fil: Mulligan, Peter. Harvard Medical School; Estados Unidos
Fil: Sebastián, Carlos. Harvard Medical School; Estados Unidos
Fil: Cosentino, Claudia. Harvard Medical School; Estados Unidos
Fil: Martínez Pastor, Bárbara. Harvard Medical School; Estados Unidos
Fil: Giacosa, Sofia. Harvard Medical School; Estados Unidos
Fil: D´Urso, Agustina. Harvard Medical School; Estados Unidos
Fil: Näär, Anders M.. Harvard Medical School; Estados Unidos
Fil: Kingston, Robert. Harvard Medical School; Estados Unidos
Fil: Rippe, Karsten. Harvard Medical School; Estados Unidos
Fil: Mostoslavsky, Raul. Harvard Medical School; Estados Unidos
Materia
Sirt6
Cromatina
Epigenetica
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/8367
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/8367
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling SIRT6 recruits SNF2H to sites of DNA breaks, preventing genomic instability through chromatin remodelingToiber, DeborahErdel, FabianBouazoune, KarimSilberman, Dafne MagaliZhong, LeiMulligan, PeterSebastián, CarlosCosentino, ClaudiaMartínez Pastor, BárbaraGiacosa, SofiaD´Urso, AgustinaNäär, Anders M.Kingston, RobertRippe, KarstenMostoslavsky, RaulSirt6CromatinaEpigeneticahttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3DNA damage is linked to multiple human diseases, such as cancer, neurodegeneration, and aging. Little is known about the role of chromatin accessibility in DNA repair. Here, we find that the deacetylase sirtuin 6 (SIRT6) is one of the earliest factors recruited to double-strand breaks (DSBs). SIRT6 recruits the chromatin remodeler SNF2H to DSBs and focally deacetylates histone H3K56. Lack of SIRT6 and SNF2H impairs chromatin remodeling, increasing sensitivity to genotoxic damage and recruitment of downstream factors such as 53BP1 and breast cancer 1 (BRCA1). Remarkably, SIRT6-deficient mice exhibit lower levels of chromatin-associated SNF2H in specific tissues, a phenotype accompanied by DNA damage. We demonstrate that SIRT6 is critical for recruitment of a chromatin remodeler as an early step in the DNA damage response, indicating that proper unfolding of chromatin plays a rate-limiting role. We present a unique crosstalk between a histone modifier and a chromatin remodeler, regulating a coordinated response to prevent DNA damage.Fil: Toiber, Deborah. Harvard Medical School; Estados UnidosFil: Erdel, Fabian. Deutsches Krebsforschungszentrum; AlemaniaFil: Bouazoune, Karim. Harvard Medical School; Estados UnidosFil: Silberman, Dafne Magali. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Harvard Medical School; Estados UnidosFil: Zhong, Lei. Harvard Medical School; Estados UnidosFil: Mulligan, Peter. Harvard Medical School; Estados UnidosFil: Sebastián, Carlos. Harvard Medical School; Estados UnidosFil: Cosentino, Claudia. Harvard Medical School; Estados UnidosFil: Martínez Pastor, Bárbara. Harvard Medical School; Estados UnidosFil: Giacosa, Sofia. Harvard Medical School; Estados UnidosFil: D´Urso, Agustina. Harvard Medical School; Estados UnidosFil: Näär, Anders M.. Harvard Medical School; Estados UnidosFil: Kingston, Robert. Harvard Medical School; Estados UnidosFil: Rippe, Karsten. Harvard Medical School; Estados UnidosFil: Mostoslavsky, Raul. Harvard Medical School; Estados UnidosCell Press2013-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/8367Toiber, Deborah; Erdel, Fabian; Bouazoune, Karim; Silberman, Dafne Magali; Zhong, Lei; et al.; SIRT6 recruits SNF2H to sites of DNA breaks, preventing genomic instability through chromatin remodeling; Cell Press; Molecular Cell; 51; 4; 8-2013; 454-4681097-2765enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1097276513004759info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3761390/info:eu-repo/semantics/altIdentifier/doi/10.1016/j.molcel.2013.06.018info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:36:58Zoai:ri.conicet.gov.ar:11336/8367instacron: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 09:36:58.76CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv SIRT6 recruits SNF2H to sites of DNA breaks, preventing genomic instability through chromatin remodeling
title SIRT6 recruits SNF2H to sites of DNA breaks, preventing genomic instability through chromatin remodeling
spellingShingle SIRT6 recruits SNF2H to sites of DNA breaks, preventing genomic instability through chromatin remodeling
Toiber, Deborah
Sirt6
Cromatina
Epigenetica
title_short SIRT6 recruits SNF2H to sites of DNA breaks, preventing genomic instability through chromatin remodeling
title_full SIRT6 recruits SNF2H to sites of DNA breaks, preventing genomic instability through chromatin remodeling
title_fullStr SIRT6 recruits SNF2H to sites of DNA breaks, preventing genomic instability through chromatin remodeling
title_full_unstemmed SIRT6 recruits SNF2H to sites of DNA breaks, preventing genomic instability through chromatin remodeling
title_sort SIRT6 recruits SNF2H to sites of DNA breaks, preventing genomic instability through chromatin remodeling
dc.creator.none.fl_str_mv Toiber, Deborah
Erdel, Fabian
Bouazoune, Karim
Silberman, Dafne Magali
Zhong, Lei
Mulligan, Peter
Sebastián, Carlos
Cosentino, Claudia
Martínez Pastor, Bárbara
Giacosa, Sofia
D´Urso, Agustina
Näär, Anders M.
Kingston, Robert
Rippe, Karsten
Mostoslavsky, Raul
author Toiber, Deborah
author_facet Toiber, Deborah
Erdel, Fabian
Bouazoune, Karim
Silberman, Dafne Magali
Zhong, Lei
Mulligan, Peter
Sebastián, Carlos
Cosentino, Claudia
Martínez Pastor, Bárbara
Giacosa, Sofia
D´Urso, Agustina
Näär, Anders M.
Kingston, Robert
Rippe, Karsten
Mostoslavsky, Raul
author_role author
author2 Erdel, Fabian
Bouazoune, Karim
Silberman, Dafne Magali
Zhong, Lei
Mulligan, Peter
Sebastián, Carlos
Cosentino, Claudia
Martínez Pastor, Bárbara
Giacosa, Sofia
D´Urso, Agustina
Näär, Anders M.
Kingston, Robert
Rippe, Karsten
Mostoslavsky, Raul
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Sirt6
Cromatina
Epigenetica
topic Sirt6
Cromatina
Epigenetica
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv DNA damage is linked to multiple human diseases, such as cancer, neurodegeneration, and aging. Little is known about the role of chromatin accessibility in DNA repair. Here, we find that the deacetylase sirtuin 6 (SIRT6) is one of the earliest factors recruited to double-strand breaks (DSBs). SIRT6 recruits the chromatin remodeler SNF2H to DSBs and focally deacetylates histone H3K56. Lack of SIRT6 and SNF2H impairs chromatin remodeling, increasing sensitivity to genotoxic damage and recruitment of downstream factors such as 53BP1 and breast cancer 1 (BRCA1). Remarkably, SIRT6-deficient mice exhibit lower levels of chromatin-associated SNF2H in specific tissues, a phenotype accompanied by DNA damage. We demonstrate that SIRT6 is critical for recruitment of a chromatin remodeler as an early step in the DNA damage response, indicating that proper unfolding of chromatin plays a rate-limiting role. We present a unique crosstalk between a histone modifier and a chromatin remodeler, regulating a coordinated response to prevent DNA damage.
Fil: Toiber, Deborah. Harvard Medical School; Estados Unidos
Fil: Erdel, Fabian. Deutsches Krebsforschungszentrum; Alemania
Fil: Bouazoune, Karim. Harvard Medical School; Estados Unidos
Fil: Silberman, Dafne Magali. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Harvard Medical School; Estados Unidos
Fil: Zhong, Lei. Harvard Medical School; Estados Unidos
Fil: Mulligan, Peter. Harvard Medical School; Estados Unidos
Fil: Sebastián, Carlos. Harvard Medical School; Estados Unidos
Fil: Cosentino, Claudia. Harvard Medical School; Estados Unidos
Fil: Martínez Pastor, Bárbara. Harvard Medical School; Estados Unidos
Fil: Giacosa, Sofia. Harvard Medical School; Estados Unidos
Fil: D´Urso, Agustina. Harvard Medical School; Estados Unidos
Fil: Näär, Anders M.. Harvard Medical School; Estados Unidos
Fil: Kingston, Robert. Harvard Medical School; Estados Unidos
Fil: Rippe, Karsten. Harvard Medical School; Estados Unidos
Fil: Mostoslavsky, Raul. Harvard Medical School; Estados Unidos
description DNA damage is linked to multiple human diseases, such as cancer, neurodegeneration, and aging. Little is known about the role of chromatin accessibility in DNA repair. Here, we find that the deacetylase sirtuin 6 (SIRT6) is one of the earliest factors recruited to double-strand breaks (DSBs). SIRT6 recruits the chromatin remodeler SNF2H to DSBs and focally deacetylates histone H3K56. Lack of SIRT6 and SNF2H impairs chromatin remodeling, increasing sensitivity to genotoxic damage and recruitment of downstream factors such as 53BP1 and breast cancer 1 (BRCA1). Remarkably, SIRT6-deficient mice exhibit lower levels of chromatin-associated SNF2H in specific tissues, a phenotype accompanied by DNA damage. We demonstrate that SIRT6 is critical for recruitment of a chromatin remodeler as an early step in the DNA damage response, indicating that proper unfolding of chromatin plays a rate-limiting role. We present a unique crosstalk between a histone modifier and a chromatin remodeler, regulating a coordinated response to prevent DNA damage.
publishDate 2013
dc.date.none.fl_str_mv 2013-08
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/11336/8367
Toiber, Deborah; Erdel, Fabian; Bouazoune, Karim; Silberman, Dafne Magali; Zhong, Lei; et al.; SIRT6 recruits SNF2H to sites of DNA breaks, preventing genomic instability through chromatin remodeling; Cell Press; Molecular Cell; 51; 4; 8-2013; 454-468
1097-2765
url http://hdl.handle.net/11336/8367
identifier_str_mv Toiber, Deborah; Erdel, Fabian; Bouazoune, Karim; Silberman, Dafne Magali; Zhong, Lei; et al.; SIRT6 recruits SNF2H to sites of DNA breaks, preventing genomic instability through chromatin remodeling; Cell Press; Molecular Cell; 51; 4; 8-2013; 454-468
1097-2765
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1097276513004759
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3761390/
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.molcel.2013.06.018
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
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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score 13.070432

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