Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/267421
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Motif WFYY of human PrimPol is crucial to stabilize the incoming 3′-nucleotide during replication fork restart |
Autor: | Calvo, Patricia A.; Martínez-Jiménez, María I. CSIC ORCID ; Díaz, Marcos; Stojkovic, Gorazd; Kasho, Kazutoshi; Guerra, Susana; Wanrooij, Sjoerd; Méndez, Juan; Blanco, Luis CSIC ORCID | Fecha de publicación: | 12-jul-2021 | Editor: | Oxford University Press | Citación: | Nucleic Acids Research 49: 8199- 8213 (2021) | Resumen: | PrimPol is the second primase in human cells, the first with the ability to start DNA chains with dNTPs. PrimPol contributes to DNA damage tolerance by restarting DNA synthesis beyond stalling lesions, acting as a TLS primase. Multiple alignment of eukaryotic PrimPols allowed us to identify a highly conserved motif, WxxY near the invariant motif A, which contains two active site metal ligands in all members of the archeo-eukaryotic primase (AEP) superfamily. In vivo and in vitro analysis of single variants of the WFYY motif of human PrimPol demonstrated that the invariant Trp87 and Tyr90 residues are essential for both primase and polymerase activities, mainly due to their crucial role in binding incoming nucleotides. Accordingly, the human variant F88L, altering the WFYY motif, displayed reduced binding of incoming nucleotides, affecting its primase/polymerase activities especially during TLS reactions on UV-damaged DNA. Conversely, the Y89D mutation initially associated with High Myopia did not affect the ability to rescue stalled replication forks in human cells. Collectively, our data suggest that the WFYY motif has a fundamental role in stabilizing the incoming 3′-nucleotide, an essential requisite for both its primase and TLS abilities during replication fork restart. | Versión del editor: | http://dx.doi.org/10.1093/nar/gkab634 | URI: | http://hdl.handle.net/10261/267421 | DOI: | 10.1093/nar/gkab634 | Identificadores: | doi: 10.1093/nar/gkab634 issn: 1362-4962 |
Aparece en las colecciones: | (CBM) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
BlancoL_Motif WFYYofHumanPrimPol.pdf | 4,19 MB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
SCOPUSTM
Citations
3
checked on 13-abr-2024
WEB OF SCIENCETM
Citations
2
checked on 19-feb-2024
Page view(s)
26
checked on 18-abr-2024
Download(s)
27
checked on 18-abr-2024
Google ScholarTM
Check
Altmetric
Altmetric
Este item está licenciado bajo una Licencia Creative Commons