Role of H4K16 acetylation in 53BP1 recruitment to double-strand break sites in in vitro aged cells

Increased frequency of DNA double strand breaks (DSBs) with aging suggests an age-associated decline in DSB repair efficiency, which is also influenced by the epigenetic landscape. H4 acetylation at lysine 16 (H4K16Ac) has been related to DSB repair since deacetylation of this mark is required for e...

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Autores: González-Bermúdez, Lourdes|||0000-0003-2379-829X, Genescà, Anna|||0000-0002-0509-956X, Terradas, Mariona|||0000-0001-7813-1172, Martín Flix, Marta|||0000-0001-7849-3616
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:267000
Acceso en línea:https://ddd.uab.cat/record/267000
https://dx.doi.org/urn:doi:10.1007/s10522-022-09979-6
Access Level:acceso abierto
Palabra clave:H4K16 acetylation
53BP1
In vitro aging
Double strand break repair
DNA damage
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spelling Role of H4K16 acetylation in 53BP1 recruitment to double-strand break sites in in vitro aged cellsGonzález-Bermúdez, Lourdes|||0000-0003-2379-829XGenescà, Anna|||0000-0002-0509-956XTerradas, Mariona|||0000-0001-7813-1172Martín Flix, Marta|||0000-0001-7849-3616H4K16 acetylation53BP1In vitro agingDouble strand break repairDNA damageIncreased frequency of DNA double strand breaks (DSBs) with aging suggests an age-associated decline in DSB repair efficiency, which is also influenced by the epigenetic landscape. H4 acetylation at lysine 16 (H4K16Ac) has been related to DSB repair since deacetylation of this mark is required for efficient 53BP1 recruitment to DSBs. Although age-associated changes in H4K16Ac levels have been studied, their contribution to age-related DSB accumulation remains unknown. In vitro aged Human Dermal Fibroblasts (HDFs) display lower levels of H4K16A that correlate with reduced recruitment of 53BP1 to basal DSBs. Following DNA damage induction, early passage (EP) cells suffered from a transient H4K16 deacetylation that allowed proper 53BP1 recruitment to DSBs. In contrast, to reach this specific and optimum level, aged cells responded by increasing their overall lower H4K16Ac levels. Induced hyperacetylation of late passage (LP) cells using trichostatin A increased H4K16Ac levels but did not ameliorate 53BP1 recruitment. Instead, deacetylation induced by MOF silencing reduced H4K16Ac levels and compromised 53BP1 recruitment in both EP and LP cells. Age-associated decrease of H4K16Ac levels contributes to the repair defect displayed by in vitro aged cells. H4K16Ac responds to DNA damage in order to reach a specific, optimum level that allows proper 53BP1 recruitment. This response may be compromised with age, as LP cells depart from lower H4K16Ac levels. Variations in H4K16Ac following the activation of the DNA damage response and aging point at this histone mark as a key mediator between DNA repair and age-associated chromatin alterations. 22022-01-0120222022-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/267000https://dx.doi.org/urn:doi:10.1007/s10522-022-09979-6reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-503open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2670002026-06-06T12:50:31Z
dc.title.none.fl_str_mv Role of H4K16 acetylation in 53BP1 recruitment to double-strand break sites in in vitro aged cells
title Role of H4K16 acetylation in 53BP1 recruitment to double-strand break sites in in vitro aged cells
spellingShingle Role of H4K16 acetylation in 53BP1 recruitment to double-strand break sites in in vitro aged cells
González-Bermúdez, Lourdes|||0000-0003-2379-829X
H4K16 acetylation
53BP1
In vitro aging
Double strand break repair
DNA damage
title_short Role of H4K16 acetylation in 53BP1 recruitment to double-strand break sites in in vitro aged cells
title_full Role of H4K16 acetylation in 53BP1 recruitment to double-strand break sites in in vitro aged cells
title_fullStr Role of H4K16 acetylation in 53BP1 recruitment to double-strand break sites in in vitro aged cells
title_full_unstemmed Role of H4K16 acetylation in 53BP1 recruitment to double-strand break sites in in vitro aged cells
title_sort Role of H4K16 acetylation in 53BP1 recruitment to double-strand break sites in in vitro aged cells
dc.creator.none.fl_str_mv González-Bermúdez, Lourdes|||0000-0003-2379-829X
Genescà, Anna|||0000-0002-0509-956X
Terradas, Mariona|||0000-0001-7813-1172
Martín Flix, Marta|||0000-0001-7849-3616
author González-Bermúdez, Lourdes|||0000-0003-2379-829X
author_facet González-Bermúdez, Lourdes|||0000-0003-2379-829X
Genescà, Anna|||0000-0002-0509-956X
Terradas, Mariona|||0000-0001-7813-1172
Martín Flix, Marta|||0000-0001-7849-3616
author_role author
author2 Genescà, Anna|||0000-0002-0509-956X
Terradas, Mariona|||0000-0001-7813-1172
Martín Flix, Marta|||0000-0001-7849-3616
author2_role author
author
author
dc.subject.none.fl_str_mv H4K16 acetylation
53BP1
In vitro aging
Double strand break repair
DNA damage
topic H4K16 acetylation
53BP1
In vitro aging
Double strand break repair
DNA damage
description Increased frequency of DNA double strand breaks (DSBs) with aging suggests an age-associated decline in DSB repair efficiency, which is also influenced by the epigenetic landscape. H4 acetylation at lysine 16 (H4K16Ac) has been related to DSB repair since deacetylation of this mark is required for efficient 53BP1 recruitment to DSBs. Although age-associated changes in H4K16Ac levels have been studied, their contribution to age-related DSB accumulation remains unknown. In vitro aged Human Dermal Fibroblasts (HDFs) display lower levels of H4K16A that correlate with reduced recruitment of 53BP1 to basal DSBs. Following DNA damage induction, early passage (EP) cells suffered from a transient H4K16 deacetylation that allowed proper 53BP1 recruitment to DSBs. In contrast, to reach this specific and optimum level, aged cells responded by increasing their overall lower H4K16Ac levels. Induced hyperacetylation of late passage (LP) cells using trichostatin A increased H4K16Ac levels but did not ameliorate 53BP1 recruitment. Instead, deacetylation induced by MOF silencing reduced H4K16Ac levels and compromised 53BP1 recruitment in both EP and LP cells. Age-associated decrease of H4K16Ac levels contributes to the repair defect displayed by in vitro aged cells. H4K16Ac responds to DNA damage in order to reach a specific, optimum level that allows proper 53BP1 recruitment. This response may be compromised with age, as LP cells depart from lower H4K16Ac levels. Variations in H4K16Ac following the activation of the DNA damage response and aging point at this histone mark as a key mediator between DNA repair and age-associated chromatin alterations.
publishDate 2022
dc.date.none.fl_str_mv 2
2022-01-01
2022
2022-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
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://ddd.uab.cat/record/267000
https://dx.doi.org/urn:doi:10.1007/s10522-022-09979-6
url https://ddd.uab.cat/record/267000
https://dx.doi.org/urn:doi:10.1007/s10522-022-09979-6
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-503
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/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
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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