Predominant role of DNA polymerase eta and p53-dependent translesion synthesis in the survival of ultraviolet-irradiated human cells

Autores
Lerner, Leticia K.; Francisco, Guilherme; Soltys, Daniela T.; Rocha, Clarissa R.R.; Quinet, Annabel; Vessoni, Alexandre T.; Castro, Ligia P.; David, Taynah I.P.; Bustos, Silvina O.; Strauss, Bryan E.; Gottifredi, Vanesa; Stary, Anne; Sarasin, Alain; Chammas, Roger; Menck, Carlos F.M.
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Genome lesions trigger biological responses that help cells manage damaged DNA, improving cell survival. Pol eta is a translesion synthesis (TLS) polymerase that bypasses lesions that block replicative polymerases, avoiding continued stalling of replication forks, which could lead to cell death. p53 also plays an important role in preventing cell death after ultraviolet (UV) light exposure. Intriguingly, we show that p53 does so by favoring translesion DNA synthesis by pol eta. In fact, the p53-dependent induction of pol eta in normal and DNA repair-deficient XP-C human cells after UV exposure has a protective effect on cell survival after challenging UV exposures, which was absent in p53- and Pol H-silenced cells. Viability increase was associated with improved elongation of nascent DNA, indicating the protective effect was due to more efficient lesion bypass by pol eta. This protection was observed in cells proficient or deficient in nucleotide excision repair, suggesting that, from a cell survival perspective, proper bypass of DNA damage can be as relevant as removal. These results indicate p53 controls the induction of pol eta in DNA damaged human cells, resulting in improved TLS and enhancing cell tolerance to DNA damage, which parallels SOS responses in bacteria.
Fil: Lerner, Leticia K.. Universidade de Sao Paulo; Brasil
Fil: Francisco, Guilherme. Cancer Institute Of The State Of Sao Paulo; Brasil
Fil: Soltys, Daniela T.. Universidade de Sao Paulo; Brasil
Fil: Rocha, Clarissa R.R.. Universidade de Sao Paulo; Brasil
Fil: Quinet, Annabel. Universidade de Sao Paulo; Brasil
Fil: Vessoni, Alexandre T.. Universidade de Sao Paulo; Brasil
Fil: Castro, Ligia P.. Universidade de Sao Paulo; Brasil
Fil: David, Taynah I.P.. Universidade de Sao Paulo; Brasil
Fil: Bustos, Silvina O.. Cancer Institute Of The State Of Sao Paulo; Brasil
Fil: Strauss, Bryan E.. Universidade de Sao Paulo; Brasil
Fil: Gottifredi, Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina
Fil: Stary, Anne. Centre National de la Recherche Scientifique; Francia
Fil: Sarasin, Alain. Centre National de la Recherche Scientifique; Francia
Fil: Chammas, Roger. Cancer Institute Of The State Of São Paulo; Brasil
Fil: Menck, Carlos F.M.. Universidade de Sao Paulo; Brasil
Materia
p53
TRANLESION DNA SYNTHESIS
SOS RESPONSE
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:11336/52557
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/52557
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Predominant role of DNA polymerase eta and p53-dependent translesion synthesis in the survival of ultraviolet-irradiated human cellsLerner, Leticia K.Francisco, GuilhermeSoltys, Daniela T.Rocha, Clarissa R.R.Quinet, AnnabelVessoni, Alexandre T.Castro, Ligia P.David, Taynah I.P.Bustos, Silvina O.Strauss, Bryan E.Gottifredi, VanesaStary, AnneSarasin, AlainChammas, RogerMenck, Carlos F.M.p53TRANLESION DNA SYNTHESISSOS RESPONSEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Genome lesions trigger biological responses that help cells manage damaged DNA, improving cell survival. Pol eta is a translesion synthesis (TLS) polymerase that bypasses lesions that block replicative polymerases, avoiding continued stalling of replication forks, which could lead to cell death. p53 also plays an important role in preventing cell death after ultraviolet (UV) light exposure. Intriguingly, we show that p53 does so by favoring translesion DNA synthesis by pol eta. In fact, the p53-dependent induction of pol eta in normal and DNA repair-deficient XP-C human cells after UV exposure has a protective effect on cell survival after challenging UV exposures, which was absent in p53- and Pol H-silenced cells. Viability increase was associated with improved elongation of nascent DNA, indicating the protective effect was due to more efficient lesion bypass by pol eta. This protection was observed in cells proficient or deficient in nucleotide excision repair, suggesting that, from a cell survival perspective, proper bypass of DNA damage can be as relevant as removal. These results indicate p53 controls the induction of pol eta in DNA damaged human cells, resulting in improved TLS and enhancing cell tolerance to DNA damage, which parallels SOS responses in bacteria.Fil: Lerner, Leticia K.. Universidade de Sao Paulo; BrasilFil: Francisco, Guilherme. Cancer Institute Of The State Of Sao Paulo; BrasilFil: Soltys, Daniela T.. Universidade de Sao Paulo; BrasilFil: Rocha, Clarissa R.R.. Universidade de Sao Paulo; BrasilFil: Quinet, Annabel. Universidade de Sao Paulo; BrasilFil: Vessoni, Alexandre T.. Universidade de Sao Paulo; BrasilFil: Castro, Ligia P.. Universidade de Sao Paulo; BrasilFil: David, Taynah I.P.. Universidade de Sao Paulo; BrasilFil: Bustos, Silvina O.. Cancer Institute Of The State Of Sao Paulo; BrasilFil: Strauss, Bryan E.. Universidade de Sao Paulo; BrasilFil: Gottifredi, Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Stary, Anne. Centre National de la Recherche Scientifique; FranciaFil: Sarasin, Alain. Centre National de la Recherche Scientifique; FranciaFil: Chammas, Roger. Cancer Institute Of The State Of São Paulo; BrasilFil: Menck, Carlos F.M.. Universidade de Sao Paulo; BrasilOxford University Press2017-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/52557Lerner, Leticia K.; Francisco, Guilherme; Soltys, Daniela T.; Rocha, Clarissa R.R.; Quinet, Annabel; et al.; Predominant role of DNA polymerase eta and p53-dependent translesion synthesis in the survival of ultraviolet-irradiated human cells; Oxford University Press; Nucleic Acids Research; 45; 3; 2-2017; 1270-12800305-10481362-4962CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/nar/article/45/3/1270/2631187info:eu-repo/semantics/altIdentifier/doi/10.1093/nar/gkw1196info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:07:44Zoai:ri.conicet.gov.ar:11336/52557instacron: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:34982025-10-22 11:07:44.639CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Predominant role of DNA polymerase eta and p53-dependent translesion synthesis in the survival of ultraviolet-irradiated human cells
title Predominant role of DNA polymerase eta and p53-dependent translesion synthesis in the survival of ultraviolet-irradiated human cells
spellingShingle Predominant role of DNA polymerase eta and p53-dependent translesion synthesis in the survival of ultraviolet-irradiated human cells
Lerner, Leticia K.
p53
TRANLESION DNA SYNTHESIS
SOS RESPONSE
title_short Predominant role of DNA polymerase eta and p53-dependent translesion synthesis in the survival of ultraviolet-irradiated human cells
title_full Predominant role of DNA polymerase eta and p53-dependent translesion synthesis in the survival of ultraviolet-irradiated human cells
title_fullStr Predominant role of DNA polymerase eta and p53-dependent translesion synthesis in the survival of ultraviolet-irradiated human cells
title_full_unstemmed Predominant role of DNA polymerase eta and p53-dependent translesion synthesis in the survival of ultraviolet-irradiated human cells
title_sort Predominant role of DNA polymerase eta and p53-dependent translesion synthesis in the survival of ultraviolet-irradiated human cells
dc.creator.none.fl_str_mv Lerner, Leticia K.
Francisco, Guilherme
Soltys, Daniela T.
Rocha, Clarissa R.R.
Quinet, Annabel
Vessoni, Alexandre T.
Castro, Ligia P.
David, Taynah I.P.
Bustos, Silvina O.
Strauss, Bryan E.
Gottifredi, Vanesa
Stary, Anne
Sarasin, Alain
Chammas, Roger
Menck, Carlos F.M.
author Lerner, Leticia K.
author_facet Lerner, Leticia K.
Francisco, Guilherme
Soltys, Daniela T.
Rocha, Clarissa R.R.
Quinet, Annabel
Vessoni, Alexandre T.
Castro, Ligia P.
David, Taynah I.P.
Bustos, Silvina O.
Strauss, Bryan E.
Gottifredi, Vanesa
Stary, Anne
Sarasin, Alain
Chammas, Roger
Menck, Carlos F.M.
author_role author
author2 Francisco, Guilherme
Soltys, Daniela T.
Rocha, Clarissa R.R.
Quinet, Annabel
Vessoni, Alexandre T.
Castro, Ligia P.
David, Taynah I.P.
Bustos, Silvina O.
Strauss, Bryan E.
Gottifredi, Vanesa
Stary, Anne
Sarasin, Alain
Chammas, Roger
Menck, Carlos F.M.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv p53
TRANLESION DNA SYNTHESIS
SOS RESPONSE
topic p53
TRANLESION DNA SYNTHESIS
SOS RESPONSE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Genome lesions trigger biological responses that help cells manage damaged DNA, improving cell survival. Pol eta is a translesion synthesis (TLS) polymerase that bypasses lesions that block replicative polymerases, avoiding continued stalling of replication forks, which could lead to cell death. p53 also plays an important role in preventing cell death after ultraviolet (UV) light exposure. Intriguingly, we show that p53 does so by favoring translesion DNA synthesis by pol eta. In fact, the p53-dependent induction of pol eta in normal and DNA repair-deficient XP-C human cells after UV exposure has a protective effect on cell survival after challenging UV exposures, which was absent in p53- and Pol H-silenced cells. Viability increase was associated with improved elongation of nascent DNA, indicating the protective effect was due to more efficient lesion bypass by pol eta. This protection was observed in cells proficient or deficient in nucleotide excision repair, suggesting that, from a cell survival perspective, proper bypass of DNA damage can be as relevant as removal. These results indicate p53 controls the induction of pol eta in DNA damaged human cells, resulting in improved TLS and enhancing cell tolerance to DNA damage, which parallels SOS responses in bacteria.
Fil: Lerner, Leticia K.. Universidade de Sao Paulo; Brasil
Fil: Francisco, Guilherme. Cancer Institute Of The State Of Sao Paulo; Brasil
Fil: Soltys, Daniela T.. Universidade de Sao Paulo; Brasil
Fil: Rocha, Clarissa R.R.. Universidade de Sao Paulo; Brasil
Fil: Quinet, Annabel. Universidade de Sao Paulo; Brasil
Fil: Vessoni, Alexandre T.. Universidade de Sao Paulo; Brasil
Fil: Castro, Ligia P.. Universidade de Sao Paulo; Brasil
Fil: David, Taynah I.P.. Universidade de Sao Paulo; Brasil
Fil: Bustos, Silvina O.. Cancer Institute Of The State Of Sao Paulo; Brasil
Fil: Strauss, Bryan E.. Universidade de Sao Paulo; Brasil
Fil: Gottifredi, Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina
Fil: Stary, Anne. Centre National de la Recherche Scientifique; Francia
Fil: Sarasin, Alain. Centre National de la Recherche Scientifique; Francia
Fil: Chammas, Roger. Cancer Institute Of The State Of São Paulo; Brasil
Fil: Menck, Carlos F.M.. Universidade de Sao Paulo; Brasil
description Genome lesions trigger biological responses that help cells manage damaged DNA, improving cell survival. Pol eta is a translesion synthesis (TLS) polymerase that bypasses lesions that block replicative polymerases, avoiding continued stalling of replication forks, which could lead to cell death. p53 also plays an important role in preventing cell death after ultraviolet (UV) light exposure. Intriguingly, we show that p53 does so by favoring translesion DNA synthesis by pol eta. In fact, the p53-dependent induction of pol eta in normal and DNA repair-deficient XP-C human cells after UV exposure has a protective effect on cell survival after challenging UV exposures, which was absent in p53- and Pol H-silenced cells. Viability increase was associated with improved elongation of nascent DNA, indicating the protective effect was due to more efficient lesion bypass by pol eta. This protection was observed in cells proficient or deficient in nucleotide excision repair, suggesting that, from a cell survival perspective, proper bypass of DNA damage can be as relevant as removal. These results indicate p53 controls the induction of pol eta in DNA damaged human cells, resulting in improved TLS and enhancing cell tolerance to DNA damage, which parallels SOS responses in bacteria.
publishDate 2017
dc.date.none.fl_str_mv 2017-02
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/11336/52557
Lerner, Leticia K.; Francisco, Guilherme; Soltys, Daniela T.; Rocha, Clarissa R.R.; Quinet, Annabel; et al.; Predominant role of DNA polymerase eta and p53-dependent translesion synthesis in the survival of ultraviolet-irradiated human cells; Oxford University Press; Nucleic Acids Research; 45; 3; 2-2017; 1270-1280
0305-1048
1362-4962
CONICET Digital
CONICET
url http://hdl.handle.net/11336/52557
identifier_str_mv Lerner, Leticia K.; Francisco, Guilherme; Soltys, Daniela T.; Rocha, Clarissa R.R.; Quinet, Annabel; et al.; Predominant role of DNA polymerase eta and p53-dependent translesion synthesis in the survival of ultraviolet-irradiated human cells; Oxford University Press; Nucleic Acids Research; 45; 3; 2-2017; 1270-1280
0305-1048
1362-4962
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/nar/article/45/3/1270/2631187
info:eu-repo/semantics/altIdentifier/doi/10.1093/nar/gkw1196
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
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University 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
_version_ 1846781397458485248
score 12.982451

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