SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling.

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...

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Detalles Bibliográficos
Autores: Toiber, Debra, Erdel, Fabian, Bouazoune, Karim, Silberman, Dafne M, Zhong, Lei, Mulligan, Peter, Sebastian, Carlos, Cosentino, Claudia, Martinez-Pastor, Barbara, Giacosa, Sofia, D'Urso, Agustina, Näär, Anders M, Kingston, Robert, Rippe, Karsten, Mostoslavsky, Raul
Tipo de recurso: artículo
Fecha de publicación:2013
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/26215
Acceso en línea:https://hdl.handle.net/20.500.12105/26215
Access Level:acceso abierto
Palabra clave:HISTONE DEACETYLASE
SIRT6
DOUBLE-STRAND
BREAKS
HOMOLOGOUS RECOMBINATION
DAMAGE
RESPONSEFACTOR
CHD4
HUMAN-CELLS
REPAIR
ACETYLATION
RESECTIONH3
id ES_ca4f6911ff3dd9c3db3ea5780bfa0772
oai_identifier_str oai:repisalud.isciii.es:20.500.12105/26215
network_acronym_str ES
network_name_str España
repository_id_str
spelling SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling.Toiber, DebraErdel, FabianBouazoune, KarimSilberman, Dafne MZhong, LeiMulligan, PeterSebastian, CarlosCosentino, ClaudiaMartinez-Pastor, BarbaraGiacosa, SofiaD'Urso, AgustinaNäär, Anders MKingston, RobertRippe, KarstenMostoslavsky, RaulHISTONE DEACETYLASESIRT6DOUBLE-STRANDBREAKSHOMOLOGOUS RECOMBINATIONDAMAGERESPONSEFACTORCHD4HUMAN-CELLSREPAIRACETYLATIONRESECTIONH3DNA 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.Cell Press20252025-01-3120132013-08-2220132013-08-22research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.12105/26215reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/262152026-06-12T12:43:37Z
dc.title.none.fl_str_mv SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling.
title SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling.
spellingShingle SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling.
Toiber, Debra
HISTONE DEACETYLASE
SIRT6
DOUBLE-STRAND
BREAKS
HOMOLOGOUS RECOMBINATION
DAMAGE
RESPONSEFACTOR
CHD4
HUMAN-CELLS
REPAIR
ACETYLATION
RESECTIONH3
title_short SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling.
title_full SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling.
title_fullStr SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling.
title_full_unstemmed SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling.
title_sort SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling.
dc.creator.none.fl_str_mv Toiber, Debra
Erdel, Fabian
Bouazoune, Karim
Silberman, Dafne M
Zhong, Lei
Mulligan, Peter
Sebastian, Carlos
Cosentino, Claudia
Martinez-Pastor, Barbara
Giacosa, Sofia
D'Urso, Agustina
Näär, Anders M
Kingston, Robert
Rippe, Karsten
Mostoslavsky, Raul
author Toiber, Debra
author_facet Toiber, Debra
Erdel, Fabian
Bouazoune, Karim
Silberman, Dafne M
Zhong, Lei
Mulligan, Peter
Sebastian, Carlos
Cosentino, Claudia
Martinez-Pastor, Barbara
Giacosa, Sofia
D'Urso, Agustina
Näär, Anders M
Kingston, Robert
Rippe, Karsten
Mostoslavsky, Raul
author_role author
author2 Erdel, Fabian
Bouazoune, Karim
Silberman, Dafne M
Zhong, Lei
Mulligan, Peter
Sebastian, Carlos
Cosentino, Claudia
Martinez-Pastor, Barbara
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.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv HISTONE DEACETYLASE
SIRT6
DOUBLE-STRAND
BREAKS
HOMOLOGOUS RECOMBINATION
DAMAGE
RESPONSEFACTOR
CHD4
HUMAN-CELLS
REPAIR
ACETYLATION
RESECTIONH3
topic HISTONE DEACETYLASE
SIRT6
DOUBLE-STRAND
BREAKS
HOMOLOGOUS RECOMBINATION
DAMAGE
RESPONSEFACTOR
CHD4
HUMAN-CELLS
REPAIR
ACETYLATION
RESECTIONH3
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
2013-08-22
2013
2013-08-22
2025
2025-01-31
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.12105/26215
url https://hdl.handle.net/20.500.12105/26215
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869419468370739200
score 15,81155

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