The levels of p53 govern the hierarchy of DNA damage tolerance pathway usage

Autores
Castaño, Bryan A.; Schorer, Sabrina; Guo, Yitian; Calzetta, Nicolás Luis; Gottifredi, Vanesa; Wiesmüller, Lisa; Biber, Stephanie
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
It is well-established that, through canonical functions in transcription and DNA repair, the tumor suppressor p53 plays a central role in safeguarding cells from the consequences of DNA damage. Recent data retrieved in tumor and stem cells demonstrated that p53 also carries out non-canonical functions when interacting with the translesion synthesis (TLS) polymerase iota (POLι) at DNA replication forks. This protein complex triggers a DNA damage tolerance (DDT) mechanism controlling the DNA replication rate. Given that the levels of p53 trigger non-binary rheostat-like functions in response to stress or during differentiation, we explore the relevance of the p53 levels for its DDT functions at the fork. We show that subtle changes in p53 levels modulate the contribution of some DDT factors including POLι, POLη, POLζ, REV1, PCNA, PRIMPOL, HLTF and ZRANB3 to the DNA replication rate. Our results suggest that the levels of p53 are central to coordinate the balance between DDT pathways including (i) fork-deceleration by the ZRANB3-mediated fork reversal factor, (ii) POLι-p53-mediated fork-slowing, (iii) POLι- and POLη-mediated TLS and (iv) PRIMPOL-mediated fork-acceleration. Collectively, our study reveals the relevance of p53 protein levels for the DDT pathway choice in replicating cells.
Fil: Castaño, Bryan A.. Universitat Ulm; Alemania
Fil: Schorer, Sabrina. Universitat Ulm; Alemania
Fil: Guo, Yitian. Universitat Ulm; Alemania
Fil: Calzetta, Nicolás Luis. 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
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
Fil: Wiesmüller, Lisa. Universitat Ulm; Alemania
Fil: Biber, Stephanie. Universitat Ulm; Alemania
Materia
p53
POL iota
translesion synthesis
PRIMPOL
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:11336/261691
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/261691
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The levels of p53 govern the hierarchy of DNA damage tolerance pathway usageCastaño, Bryan A.Schorer, SabrinaGuo, YitianCalzetta, Nicolás LuisGottifredi, VanesaWiesmüller, LisaBiber, Stephaniep53POL iotatranslesion synthesisPRIMPOLhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1It is well-established that, through canonical functions in transcription and DNA repair, the tumor suppressor p53 plays a central role in safeguarding cells from the consequences of DNA damage. Recent data retrieved in tumor and stem cells demonstrated that p53 also carries out non-canonical functions when interacting with the translesion synthesis (TLS) polymerase iota (POLι) at DNA replication forks. This protein complex triggers a DNA damage tolerance (DDT) mechanism controlling the DNA replication rate. Given that the levels of p53 trigger non-binary rheostat-like functions in response to stress or during differentiation, we explore the relevance of the p53 levels for its DDT functions at the fork. We show that subtle changes in p53 levels modulate the contribution of some DDT factors including POLι, POLη, POLζ, REV1, PCNA, PRIMPOL, HLTF and ZRANB3 to the DNA replication rate. Our results suggest that the levels of p53 are central to coordinate the balance between DDT pathways including (i) fork-deceleration by the ZRANB3-mediated fork reversal factor, (ii) POLι-p53-mediated fork-slowing, (iii) POLι- and POLη-mediated TLS and (iv) PRIMPOL-mediated fork-acceleration. Collectively, our study reveals the relevance of p53 protein levels for the DDT pathway choice in replicating cells.Fil: Castaño, Bryan A.. Universitat Ulm; AlemaniaFil: Schorer, Sabrina. Universitat Ulm; AlemaniaFil: Guo, Yitian. Universitat Ulm; AlemaniaFil: Calzetta, Nicolás Luis. 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; ArgentinaFil: 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; ArgentinaFil: Wiesmüller, Lisa. Universitat Ulm; AlemaniaFil: Biber, Stephanie. Universitat Ulm; AlemaniaOxford University Press2024-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/261691Castaño, Bryan A.; Schorer, Sabrina; Guo, Yitian; Calzetta, Nicolás Luis; Gottifredi, Vanesa; et al.; The levels of p53 govern the hierarchy of DNA damage tolerance pathway usage; Oxford University Press; Nucleic Acids Research; 52; 7; 2-2024; 3740-37600305-10481362-4962CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkae061/7600450info:eu-repo/semantics/altIdentifier/doi/10.1093/nar/gkae061info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-05T10:23:37Zoai:ri.conicet.gov.ar:11336/261691instacron: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:34982025-11-05 10:23:37.775CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The levels of p53 govern the hierarchy of DNA damage tolerance pathway usage
title The levels of p53 govern the hierarchy of DNA damage tolerance pathway usage
spellingShingle The levels of p53 govern the hierarchy of DNA damage tolerance pathway usage
Castaño, Bryan A.
p53
POL iota
translesion synthesis
PRIMPOL
title_short The levels of p53 govern the hierarchy of DNA damage tolerance pathway usage
title_full The levels of p53 govern the hierarchy of DNA damage tolerance pathway usage
title_fullStr The levels of p53 govern the hierarchy of DNA damage tolerance pathway usage
title_full_unstemmed The levels of p53 govern the hierarchy of DNA damage tolerance pathway usage
title_sort The levels of p53 govern the hierarchy of DNA damage tolerance pathway usage
dc.creator.none.fl_str_mv Castaño, Bryan A.
Schorer, Sabrina
Guo, Yitian
Calzetta, Nicolás Luis
Gottifredi, Vanesa
Wiesmüller, Lisa
Biber, Stephanie
author Castaño, Bryan A.
author_facet Castaño, Bryan A.
Schorer, Sabrina
Guo, Yitian
Calzetta, Nicolás Luis
Gottifredi, Vanesa
Wiesmüller, Lisa
Biber, Stephanie
author_role author
author2 Schorer, Sabrina
Guo, Yitian
Calzetta, Nicolás Luis
Gottifredi, Vanesa
Wiesmüller, Lisa
Biber, Stephanie
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv p53
POL iota
translesion synthesis
PRIMPOL
topic p53
POL iota
translesion synthesis
PRIMPOL
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv It is well-established that, through canonical functions in transcription and DNA repair, the tumor suppressor p53 plays a central role in safeguarding cells from the consequences of DNA damage. Recent data retrieved in tumor and stem cells demonstrated that p53 also carries out non-canonical functions when interacting with the translesion synthesis (TLS) polymerase iota (POLι) at DNA replication forks. This protein complex triggers a DNA damage tolerance (DDT) mechanism controlling the DNA replication rate. Given that the levels of p53 trigger non-binary rheostat-like functions in response to stress or during differentiation, we explore the relevance of the p53 levels for its DDT functions at the fork. We show that subtle changes in p53 levels modulate the contribution of some DDT factors including POLι, POLη, POLζ, REV1, PCNA, PRIMPOL, HLTF and ZRANB3 to the DNA replication rate. Our results suggest that the levels of p53 are central to coordinate the balance between DDT pathways including (i) fork-deceleration by the ZRANB3-mediated fork reversal factor, (ii) POLι-p53-mediated fork-slowing, (iii) POLι- and POLη-mediated TLS and (iv) PRIMPOL-mediated fork-acceleration. Collectively, our study reveals the relevance of p53 protein levels for the DDT pathway choice in replicating cells.
Fil: Castaño, Bryan A.. Universitat Ulm; Alemania
Fil: Schorer, Sabrina. Universitat Ulm; Alemania
Fil: Guo, Yitian. Universitat Ulm; Alemania
Fil: Calzetta, Nicolás Luis. 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
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
Fil: Wiesmüller, Lisa. Universitat Ulm; Alemania
Fil: Biber, Stephanie. Universitat Ulm; Alemania
description It is well-established that, through canonical functions in transcription and DNA repair, the tumor suppressor p53 plays a central role in safeguarding cells from the consequences of DNA damage. Recent data retrieved in tumor and stem cells demonstrated that p53 also carries out non-canonical functions when interacting with the translesion synthesis (TLS) polymerase iota (POLι) at DNA replication forks. This protein complex triggers a DNA damage tolerance (DDT) mechanism controlling the DNA replication rate. Given that the levels of p53 trigger non-binary rheostat-like functions in response to stress or during differentiation, we explore the relevance of the p53 levels for its DDT functions at the fork. We show that subtle changes in p53 levels modulate the contribution of some DDT factors including POLι, POLη, POLζ, REV1, PCNA, PRIMPOL, HLTF and ZRANB3 to the DNA replication rate. Our results suggest that the levels of p53 are central to coordinate the balance between DDT pathways including (i) fork-deceleration by the ZRANB3-mediated fork reversal factor, (ii) POLι-p53-mediated fork-slowing, (iii) POLι- and POLη-mediated TLS and (iv) PRIMPOL-mediated fork-acceleration. Collectively, our study reveals the relevance of p53 protein levels for the DDT pathway choice in replicating cells.
publishDate 2024
dc.date.none.fl_str_mv 2024-02
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/11336/261691
Castaño, Bryan A.; Schorer, Sabrina; Guo, Yitian; Calzetta, Nicolás Luis; Gottifredi, Vanesa; et al.; The levels of p53 govern the hierarchy of DNA damage tolerance pathway usage; Oxford University Press; Nucleic Acids Research; 52; 7; 2-2024; 3740-3760
0305-1048
1362-4962
CONICET Digital
CONICET
url http://hdl.handle.net/11336/261691
identifier_str_mv Castaño, Bryan A.; Schorer, Sabrina; Guo, Yitian; Calzetta, Nicolás Luis; Gottifredi, Vanesa; et al.; The levels of p53 govern the hierarchy of DNA damage tolerance pathway usage; Oxford University Press; Nucleic Acids Research; 52; 7; 2-2024; 3740-3760
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/advance-article/doi/10.1093/nar/gkae061/7600450
info:eu-repo/semantics/altIdentifier/doi/10.1093/nar/gkae061
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
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_ 1847977862292832256
score 13.121305

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