Polymerase iota (Pol ι) prevents PrimPol-mediated nascent DNA synthesis and chromosome instability

Autores
Mansilla, Sabrina Florencia; Bertolin, Agostina P.; Venerus Arbilla, Sofía; Castaño, Bryan Alain Alexis; Jahjah, Tiya; Singh, Jenny K.; Siri, Sebastian Omar; Castro, María Victoria; de la Vega Páez, María Belén; Quinet, Annabel; Wiesmüller, Lisa; Gottifredi, Vanesa
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Recent studies have described a DNA damage tolerance pathway choice that involves a competition between PrimPol-mediated repriming and fork reversal. Screening different translesion DNA synthesis (TLS) polymerases by the use of tools for their depletion, we identified a unique role of Pol ι in regulating such a pathway choice. Pol ι deficiency unleashes PrimPol-dependent repriming, which accelerates DNA replication in a pathway that is epistatic with ZRANB3 knockdown. In Pol ι–depleted cells, the excess participation of PrimPol in nascent DNA elongation reduces replication stress signals, but thereby also checkpoint activation in S phase, triggering chromosome instability in M phase. This TLS-independent function of Pol ι requires its PCNA-interacting but not its polymerase domain. Our findings unravel an unanticipated role of Pol ι in protecting the genome stability of cells from detrimental changes in DNA replication dynamics caused by PrimPol.
Fil: Mansilla, Sabrina Florencia. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bertolin, Agostina P.. Fundación Instituto Leloir; Argentina. The Francis Crick Institute; Reino Unido
Fil: Venerus Arbilla, Sofía. 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: Castaño, Bryan Alain Alexis. Universitat Ulm; Alemania
Fil: Jahjah, Tiya. Universite Paris-Saclay ; . Université Paris Cité; Francia. Inserm; Francia
Fil: Singh, Jenny K.. Inserm; Francia. Université Paris Cité; Francia. Universite Paris-Saclay ;
Fil: Siri, Sebastian Omar. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Castro, María Victoria. Fundación Instituto Leloir; Argentina
Fil: de la Vega Páez, María Belén. 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: Quinet, Annabel. Université Paris Cité; Francia. Inserm; Francia. Universite Paris-Saclay ;
Fil: Wiesmüller, Lisa. Universitat Ulm; Alemania
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
Materia
Pol iota
DNA Replication
Gaps
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:11336/228785
Acceder
id CONICETDig_789743c9bedcebd0e9fe04dddd424dc6
oai_identifier_str oai:ri.conicet.gov.ar:11336/228785
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Polymerase iota (Pol ι) prevents PrimPol-mediated nascent DNA synthesis and chromosome instabilityMansilla, Sabrina FlorenciaBertolin, Agostina P.Venerus Arbilla, SofíaCastaño, Bryan Alain AlexisJahjah, TiyaSingh, Jenny K.Siri, Sebastian OmarCastro, María Victoriade la Vega Páez, María BelénQuinet, AnnabelWiesmüller, LisaGottifredi, VanesaPol iotaDNA ReplicationGapsPrimPolhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Recent studies have described a DNA damage tolerance pathway choice that involves a competition between PrimPol-mediated repriming and fork reversal. Screening different translesion DNA synthesis (TLS) polymerases by the use of tools for their depletion, we identified a unique role of Pol ι in regulating such a pathway choice. Pol ι deficiency unleashes PrimPol-dependent repriming, which accelerates DNA replication in a pathway that is epistatic with ZRANB3 knockdown. In Pol ι–depleted cells, the excess participation of PrimPol in nascent DNA elongation reduces replication stress signals, but thereby also checkpoint activation in S phase, triggering chromosome instability in M phase. This TLS-independent function of Pol ι requires its PCNA-interacting but not its polymerase domain. Our findings unravel an unanticipated role of Pol ι in protecting the genome stability of cells from detrimental changes in DNA replication dynamics caused by PrimPol.Fil: Mansilla, Sabrina Florencia. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bertolin, Agostina P.. Fundación Instituto Leloir; Argentina. The Francis Crick Institute; Reino UnidoFil: Venerus Arbilla, Sofía. 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: Castaño, Bryan Alain Alexis. Universitat Ulm; AlemaniaFil: Jahjah, Tiya. Universite Paris-Saclay ; . Université Paris Cité; Francia. Inserm; FranciaFil: Singh, Jenny K.. Inserm; Francia. Université Paris Cité; Francia. Universite Paris-Saclay ;Fil: Siri, Sebastian Omar. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Castro, María Victoria. Fundación Instituto Leloir; ArgentinaFil: de la Vega Páez, María Belén. 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: Quinet, Annabel. Université Paris Cité; Francia. Inserm; Francia. Universite Paris-Saclay ;Fil: Wiesmüller, Lisa. Universitat Ulm; AlemaniaFil: 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; ArgentinaScience Advances is the American Association for the Advancement of Science2023-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/228785Mansilla, Sabrina Florencia; Bertolin, Agostina P.; Venerus Arbilla, Sofía; Castaño, Bryan Alain Alexis; Jahjah, Tiya; et al.; Polymerase iota (Pol ι) prevents PrimPol-mediated nascent DNA synthesis and chromosome instability; Science Advances is the American Association for the Advancement of Science; Science Advances; 9; 15; 4-2023; 1-192375-2548CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1126/sciadv.ade7997info:eu-repo/semantics/altIdentifier/url/https://www.science.org/doi/10.1126/sciadv.ade7997#tab-contributorsinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T11:18:42Zoai:ri.conicet.gov.ar:11336/228785instacron: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:34982025-09-17 11:18:42.364CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Polymerase iota (Pol ι) prevents PrimPol-mediated nascent DNA synthesis and chromosome instability
title Polymerase iota (Pol ι) prevents PrimPol-mediated nascent DNA synthesis and chromosome instability
spellingShingle Polymerase iota (Pol ι) prevents PrimPol-mediated nascent DNA synthesis and chromosome instability
Mansilla, Sabrina Florencia
Pol iota
DNA Replication
Gaps
PrimPol
title_short Polymerase iota (Pol ι) prevents PrimPol-mediated nascent DNA synthesis and chromosome instability
title_full Polymerase iota (Pol ι) prevents PrimPol-mediated nascent DNA synthesis and chromosome instability
title_fullStr Polymerase iota (Pol ι) prevents PrimPol-mediated nascent DNA synthesis and chromosome instability
title_full_unstemmed Polymerase iota (Pol ι) prevents PrimPol-mediated nascent DNA synthesis and chromosome instability
title_sort Polymerase iota (Pol ι) prevents PrimPol-mediated nascent DNA synthesis and chromosome instability
dc.creator.none.fl_str_mv Mansilla, Sabrina Florencia
Bertolin, Agostina P.
Venerus Arbilla, Sofía
Castaño, Bryan Alain Alexis
Jahjah, Tiya
Singh, Jenny K.
Siri, Sebastian Omar
Castro, María Victoria
de la Vega Páez, María Belén
Quinet, Annabel
Wiesmüller, Lisa
Gottifredi, Vanesa
author Mansilla, Sabrina Florencia
author_facet Mansilla, Sabrina Florencia
Bertolin, Agostina P.
Venerus Arbilla, Sofía
Castaño, Bryan Alain Alexis
Jahjah, Tiya
Singh, Jenny K.
Siri, Sebastian Omar
Castro, María Victoria
de la Vega Páez, María Belén
Quinet, Annabel
Wiesmüller, Lisa
Gottifredi, Vanesa
author_role author
author2 Bertolin, Agostina P.
Venerus Arbilla, Sofía
Castaño, Bryan Alain Alexis
Jahjah, Tiya
Singh, Jenny K.
Siri, Sebastian Omar
Castro, María Victoria
de la Vega Páez, María Belén
Quinet, Annabel
Wiesmüller, Lisa
Gottifredi, Vanesa
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Pol iota
DNA Replication
Gaps
PrimPol
topic Pol iota
DNA Replication
Gaps
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 Recent studies have described a DNA damage tolerance pathway choice that involves a competition between PrimPol-mediated repriming and fork reversal. Screening different translesion DNA synthesis (TLS) polymerases by the use of tools for their depletion, we identified a unique role of Pol ι in regulating such a pathway choice. Pol ι deficiency unleashes PrimPol-dependent repriming, which accelerates DNA replication in a pathway that is epistatic with ZRANB3 knockdown. In Pol ι–depleted cells, the excess participation of PrimPol in nascent DNA elongation reduces replication stress signals, but thereby also checkpoint activation in S phase, triggering chromosome instability in M phase. This TLS-independent function of Pol ι requires its PCNA-interacting but not its polymerase domain. Our findings unravel an unanticipated role of Pol ι in protecting the genome stability of cells from detrimental changes in DNA replication dynamics caused by PrimPol.
Fil: Mansilla, Sabrina Florencia. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bertolin, Agostina P.. Fundación Instituto Leloir; Argentina. The Francis Crick Institute; Reino Unido
Fil: Venerus Arbilla, Sofía. 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: Castaño, Bryan Alain Alexis. Universitat Ulm; Alemania
Fil: Jahjah, Tiya. Universite Paris-Saclay ; . Université Paris Cité; Francia. Inserm; Francia
Fil: Singh, Jenny K.. Inserm; Francia. Université Paris Cité; Francia. Universite Paris-Saclay ;
Fil: Siri, Sebastian Omar. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Castro, María Victoria. Fundación Instituto Leloir; Argentina
Fil: de la Vega Páez, María Belén. 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: Quinet, Annabel. Université Paris Cité; Francia. Inserm; Francia. Universite Paris-Saclay ;
Fil: Wiesmüller, Lisa. Universitat Ulm; Alemania
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
description Recent studies have described a DNA damage tolerance pathway choice that involves a competition between PrimPol-mediated repriming and fork reversal. Screening different translesion DNA synthesis (TLS) polymerases by the use of tools for their depletion, we identified a unique role of Pol ι in regulating such a pathway choice. Pol ι deficiency unleashes PrimPol-dependent repriming, which accelerates DNA replication in a pathway that is epistatic with ZRANB3 knockdown. In Pol ι–depleted cells, the excess participation of PrimPol in nascent DNA elongation reduces replication stress signals, but thereby also checkpoint activation in S phase, triggering chromosome instability in M phase. This TLS-independent function of Pol ι requires its PCNA-interacting but not its polymerase domain. Our findings unravel an unanticipated role of Pol ι in protecting the genome stability of cells from detrimental changes in DNA replication dynamics caused by PrimPol.
publishDate 2023
dc.date.none.fl_str_mv 2023-04
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/11336/228785
Mansilla, Sabrina Florencia; Bertolin, Agostina P.; Venerus Arbilla, Sofía; Castaño, Bryan Alain Alexis; Jahjah, Tiya; et al.; Polymerase iota (Pol ι) prevents PrimPol-mediated nascent DNA synthesis and chromosome instability; Science Advances is the American Association for the Advancement of Science; Science Advances; 9; 15; 4-2023; 1-19
2375-2548
CONICET Digital
CONICET
url http://hdl.handle.net/11336/228785
identifier_str_mv Mansilla, Sabrina Florencia; Bertolin, Agostina P.; Venerus Arbilla, Sofía; Castaño, Bryan Alain Alexis; Jahjah, Tiya; et al.; Polymerase iota (Pol ι) prevents PrimPol-mediated nascent DNA synthesis and chromosome instability; Science Advances is the American Association for the Advancement of Science; Science Advances; 9; 15; 4-2023; 1-19
2375-2548
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1126/sciadv.ade7997
info:eu-repo/semantics/altIdentifier/url/https://www.science.org/doi/10.1126/sciadv.ade7997#tab-contributors
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
dc.publisher.none.fl_str_mv Science Advances is the American Association for the Advancement of Science
publisher.none.fl_str_mv Science Advances is the American Association for the Advancement of Science
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_ 1843606531329753088
score 13.000565

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