PCNA molecular recognition of different PIP motifs: Role of Tyr211 phosphorylation

The coordination of enzymes and regulatory proteins for eukaryotic DNA replication and repair is largely achieved by Proliferating Cell Nuclear Antigen (PCNA), a toroidal homotrimeric protein that embraces the DNA duplex. Many proteins bind PCNA through a conserved sequence known as the PCNA interac...

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Detalles Bibliográficos
Autores: Ruiz Albor, Antonio, Chaves Arquero, Belén, Martín Barros, Inés, Guerra Castellano, Alejandra, González-Magaña, Amaia, Ibáñez de Okapua, Alain, Merino, Nekane, Ferreras Gutiérrez, Mariola, Berra, Edurne, Díaz Moreno, Irene, Blanco, Francisco J.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/161486
Acceso en línea:https://hdl.handle.net/11441/161486
https://doi.org/10.1016/j.ijbiomac.2024.133187
Access Level:acceso abierto
Palabra clave:DNA replication
Molecular recognition
PCNA
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spelling PCNA molecular recognition of different PIP motifs: Role of Tyr211 phosphorylationRuiz Albor, AntonioChaves Arquero, BelénMartín Barros, InésGuerra Castellano, AlejandraGonzález-Magaña, AmaiaIbáñez de Okapua, AlainMerino, NekaneFerreras Gutiérrez, MariolaBerra, EdurneDíaz Moreno, IreneBlanco, Francisco J.DNA replicationMolecular recognitionPCNAThe coordination of enzymes and regulatory proteins for eukaryotic DNA replication and repair is largely achieved by Proliferating Cell Nuclear Antigen (PCNA), a toroidal homotrimeric protein that embraces the DNA duplex. Many proteins bind PCNA through a conserved sequence known as the PCNA interacting protein motif (PIP). PCNA is further regulated by different post-translational modifications. Phosphorylation at residue Y211 facilitates unlocking stalled replication forks to bypass DNA damage repair processes but increasing nucleotide misincorporation. We explore here how phosphorylation at Y211 affects PCNA recognition of the canonical PIP sequences of the regulatory proteins p21 and p15, which bind with nM and μM affinity, respectively. For that purpose, we have prepared PCNA with p-carboxymethyl-L-phenylalanine (pCMF, a mimetic of phosphorylated tyrosine) at position 211. We have also characterized PCNA binding to the non-canonical PIP sequence of the catalytic subunit of DNA polymerase δ (p125), and to the canonical PIP sequence of the enzyme ubiquitin specific peptidase 29 (USP29) which deubiquitinates PCNA. Our results show that Tyr211 phosphorylation has little effect on the molecular recognition of p21 and p15, and that the PIP sequences of p125 and USP29 bind to the same site on PCNA as other PIP sequences, but with very low affinity.Ministerio de Ciencia e Innovación PID2020-113225GB-I00, PID2021-126663NB-I00, PRE2021-099992, PRE2018-085788Junta de Andalucía BIO-198Consejo Superior de Investigaciones Científicas (CSIC) PIE202120E047ElsevierBioquímica Vegetal y Biología MolecularMinisterio de Ciencia e Innovación (MICIN). EspañaJunta de AndalucíaConsejo Superior de Investigaciones Científicas (CSIC)2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/161486https://doi.org/10.1016/j.ijbiomac.2024.133187reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésInternational Journal of Biological Macromolecules, 273 (2), 133187.PID2020-113225GB-I00PID2021-126663NB-I00PRE2021-099992PRE2018-085788BIO-198PIE202120E047https://doi.org/10.1016/j.ijbiomac.2024.133187info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1614862026-06-17T12:51:07Z
dc.title.none.fl_str_mv PCNA molecular recognition of different PIP motifs: Role of Tyr211 phosphorylation
title PCNA molecular recognition of different PIP motifs: Role of Tyr211 phosphorylation
spellingShingle PCNA molecular recognition of different PIP motifs: Role of Tyr211 phosphorylation
Ruiz Albor, Antonio
DNA replication
Molecular recognition
PCNA
title_short PCNA molecular recognition of different PIP motifs: Role of Tyr211 phosphorylation
title_full PCNA molecular recognition of different PIP motifs: Role of Tyr211 phosphorylation
title_fullStr PCNA molecular recognition of different PIP motifs: Role of Tyr211 phosphorylation
title_full_unstemmed PCNA molecular recognition of different PIP motifs: Role of Tyr211 phosphorylation
title_sort PCNA molecular recognition of different PIP motifs: Role of Tyr211 phosphorylation
dc.creator.none.fl_str_mv Ruiz Albor, Antonio
Chaves Arquero, Belén
Martín Barros, Inés
Guerra Castellano, Alejandra
González-Magaña, Amaia
Ibáñez de Okapua, Alain
Merino, Nekane
Ferreras Gutiérrez, Mariola
Berra, Edurne
Díaz Moreno, Irene
Blanco, Francisco J.
author Ruiz Albor, Antonio
author_facet Ruiz Albor, Antonio
Chaves Arquero, Belén
Martín Barros, Inés
Guerra Castellano, Alejandra
González-Magaña, Amaia
Ibáñez de Okapua, Alain
Merino, Nekane
Ferreras Gutiérrez, Mariola
Berra, Edurne
Díaz Moreno, Irene
Blanco, Francisco J.
author_role author
author2 Chaves Arquero, Belén
Martín Barros, Inés
Guerra Castellano, Alejandra
González-Magaña, Amaia
Ibáñez de Okapua, Alain
Merino, Nekane
Ferreras Gutiérrez, Mariola
Berra, Edurne
Díaz Moreno, Irene
Blanco, Francisco J.
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Bioquímica Vegetal y Biología Molecular
Ministerio de Ciencia e Innovación (MICIN). España
Junta de Andalucía
Consejo Superior de Investigaciones Científicas (CSIC)
dc.subject.none.fl_str_mv DNA replication
Molecular recognition
PCNA
topic DNA replication
Molecular recognition
PCNA
description The coordination of enzymes and regulatory proteins for eukaryotic DNA replication and repair is largely achieved by Proliferating Cell Nuclear Antigen (PCNA), a toroidal homotrimeric protein that embraces the DNA duplex. Many proteins bind PCNA through a conserved sequence known as the PCNA interacting protein motif (PIP). PCNA is further regulated by different post-translational modifications. Phosphorylation at residue Y211 facilitates unlocking stalled replication forks to bypass DNA damage repair processes but increasing nucleotide misincorporation. We explore here how phosphorylation at Y211 affects PCNA recognition of the canonical PIP sequences of the regulatory proteins p21 and p15, which bind with nM and μM affinity, respectively. For that purpose, we have prepared PCNA with p-carboxymethyl-L-phenylalanine (pCMF, a mimetic of phosphorylated tyrosine) at position 211. We have also characterized PCNA binding to the non-canonical PIP sequence of the catalytic subunit of DNA polymerase δ (p125), and to the canonical PIP sequence of the enzyme ubiquitin specific peptidase 29 (USP29) which deubiquitinates PCNA. Our results show that Tyr211 phosphorylation has little effect on the molecular recognition of p21 and p15, and that the PIP sequences of p125 and USP29 bind to the same site on PCNA as other PIP sequences, but with very low affinity.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/161486
https://doi.org/10.1016/j.ijbiomac.2024.133187
url https://hdl.handle.net/11441/161486
https://doi.org/10.1016/j.ijbiomac.2024.133187
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv International Journal of Biological Macromolecules, 273 (2), 133187.
PID2020-113225GB-I00
PID2021-126663NB-I00
PRE2021-099992
PRE2018-085788
BIO-198
PIE202120E047
https://doi.org/10.1016/j.ijbiomac.2024.133187
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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