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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/52557
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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 Técnicas2025-09-29T09:39:21Zoai: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:34982025-09-29 09:39:21.536CONICET 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_ |
1844613245320560640 |
score |
13.070432 |