RanBP2-Mediated SUMOylation Promotes Human DNA Polymerase Lambda Nuclear Localization and DNA Repair.

Cellular DNA is under constant attack by a wide variety of agents, both endogenous and exogenous. To counteract DNA damage, human cells have a large collection of DNA repair factors. Among them, DNA polymerase lambda (Polλ) stands out for its versatility, as it participates in different DNA repair a...

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Detalles Bibliográficos
Autores: Moreno-Oñate, M, Herrero-Ruiz, A M, García-Dominguez, M, Cortes-Ledesma, Felipe, Ruiz, J F
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/25359
Acceso en línea:https://hdl.handle.net/20.500.12105/25359
Access Level:acceso abierto
Palabra clave:DNA polymerase lambda
DNA repair
SUMOylation
post-translational modifications
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spelling RanBP2-Mediated SUMOylation Promotes Human DNA Polymerase Lambda Nuclear Localization and DNA Repair.Moreno-Oñate, MHerrero-Ruiz, A MGarcía-Dominguez, MCortes-Ledesma, FelipeRuiz, J FDNA polymerase lambdaDNA repairSUMOylationpost-translational modificationsCellular DNA is under constant attack by a wide variety of agents, both endogenous and exogenous. To counteract DNA damage, human cells have a large collection of DNA repair factors. Among them, DNA polymerase lambda (Polλ) stands out for its versatility, as it participates in different DNA repair and damage tolerance pathways in which gap-filling DNA synthesis is required. In this work, we show that human Polλ is conjugated with Small Ubiquitin-like MOdifier (SUMO) proteins both in vitro and in vivo, with Lys27 being the main target of this covalent modification. Polλ SUMOylation takes place in the nuclear pore complex and is mediated by the E3 ligase RanBP2. This post-translational modification promotes Polλ entry into the nucleus, which is required for its recruitment to DNA lesions and stimulated by DNA damage induction. Our work represents an advance in the knowledge of molecular pathways that regulate cellular localization of human Polλ, which are essential to be able to perform its functions during repair of nuclear DNA, and that might constitute an important point for the modulation of its activity in human cells.ElsevierMinisterio de Economía y Competitividad (España)Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Unión Europea. Comisión Europea. European Research Council (ERC)Universidad de Sevilla (España)20242024-10-2920202020-06-1220202020-06-12research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.12105/25359reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengMinisterio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 Not available BFU2013-44343-P BASES MOLECULARES DE LA FORMACION DE TRANSLOCACIONES CROMOSOMICAS POTENCIALMENTE ONCOGENICAS POR NHEJ. PAPEL Y REGULACION DE LAS POLX HUMANASMinisterio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 Not available RYC-2011-08752 RYC-2011-08752open accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/253592026-06-12T12:43:37Z
dc.title.none.fl_str_mv RanBP2-Mediated SUMOylation Promotes Human DNA Polymerase Lambda Nuclear Localization and DNA Repair.
title RanBP2-Mediated SUMOylation Promotes Human DNA Polymerase Lambda Nuclear Localization and DNA Repair.
spellingShingle RanBP2-Mediated SUMOylation Promotes Human DNA Polymerase Lambda Nuclear Localization and DNA Repair.
Moreno-Oñate, M
DNA polymerase lambda
DNA repair
SUMOylation
post-translational modifications
title_short RanBP2-Mediated SUMOylation Promotes Human DNA Polymerase Lambda Nuclear Localization and DNA Repair.
title_full RanBP2-Mediated SUMOylation Promotes Human DNA Polymerase Lambda Nuclear Localization and DNA Repair.
title_fullStr RanBP2-Mediated SUMOylation Promotes Human DNA Polymerase Lambda Nuclear Localization and DNA Repair.
title_full_unstemmed RanBP2-Mediated SUMOylation Promotes Human DNA Polymerase Lambda Nuclear Localization and DNA Repair.
title_sort RanBP2-Mediated SUMOylation Promotes Human DNA Polymerase Lambda Nuclear Localization and DNA Repair.
dc.creator.none.fl_str_mv Moreno-Oñate, M
Herrero-Ruiz, A M
García-Dominguez, M
Cortes-Ledesma, Felipe
Ruiz, J F
author Moreno-Oñate, M
author_facet Moreno-Oñate, M
Herrero-Ruiz, A M
García-Dominguez, M
Cortes-Ledesma, Felipe
Ruiz, J F
author_role author
author2 Herrero-Ruiz, A M
García-Dominguez, M
Cortes-Ledesma, Felipe
Ruiz, J F
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Unión Europea. Comisión Europea. European Research Council (ERC)
Universidad de Sevilla (España)
dc.subject.none.fl_str_mv DNA polymerase lambda
DNA repair
SUMOylation
post-translational modifications
topic DNA polymerase lambda
DNA repair
SUMOylation
post-translational modifications
description Cellular DNA is under constant attack by a wide variety of agents, both endogenous and exogenous. To counteract DNA damage, human cells have a large collection of DNA repair factors. Among them, DNA polymerase lambda (Polλ) stands out for its versatility, as it participates in different DNA repair and damage tolerance pathways in which gap-filling DNA synthesis is required. In this work, we show that human Polλ is conjugated with Small Ubiquitin-like MOdifier (SUMO) proteins both in vitro and in vivo, with Lys27 being the main target of this covalent modification. Polλ SUMOylation takes place in the nuclear pore complex and is mediated by the E3 ligase RanBP2. This post-translational modification promotes Polλ entry into the nucleus, which is required for its recruitment to DNA lesions and stimulated by DNA damage induction. Our work represents an advance in the knowledge of molecular pathways that regulate cellular localization of human Polλ, which are essential to be able to perform its functions during repair of nuclear DNA, and that might constitute an important point for the modulation of its activity in human cells.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-06-12
2020
2020-06-12
2024
2024-10-29
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/20.500.12105/25359
url https://hdl.handle.net/20.500.12105/25359
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 Not available BFU2013-44343-P BASES MOLECULARES DE LA FORMACION DE TRANSLOCACIONES CROMOSOMICAS POTENCIALMENTE ONCOGENICAS POR NHEJ. PAPEL Y REGULACION DE LAS POLX HUMANAS
Ministerio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 Not available RYC-2011-08752 RYC-2011-08752
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://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
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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
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score 15,811543

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