Artículo
PCNA molecular recognition of different PIP motifs: Role of Tyr211 phosphorylation
Autor/es | 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. |
Departamento | Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular |
Fecha de publicación | 2024-07 |
Fecha de depósito | 2024-07-17 |
Publicado en |
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Resumen | 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. ... 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. |
Agencias financiadoras | Ministerio de Ciencia e Innovación (MICIN). España Junta de Andalucía Consejo Superior de Investigaciones Científicas (CSIC) |
Identificador del proyecto | PID2020-113225GB-I00
PID2021-126663NB-I00 PRE2021-099992 PRE2018-085788 BIO-198 PIE202120E047 |
Cita | Ruiz Albor, A., Chaves Arquero, B., Martín Barros, I., Guerra Castellano, A., González-Magaña, A., Ibáñez de Okapua, A.,...,Blanco, F.J. (2024). PCNA molecular recognition of different PIP motifs: Role of Tyr211 phosphorylation. International Journal of Biological Macromolecules, 273 (2), 133187. https://doi.org/10.1016/j.ijbiomac.2024.133187. |
Ficheros | Tamaño | Formato | Ver | Descripción |
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PCNA molecular.pdf | 6.050Mb | [PDF] | Ver/ | Versión publicada |