English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/182438
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:


The Zn-finger domain of human PrimPol is required to stabilize the initiating nucleotide during DNA priming

AuthorsMartínez-Jiménez, María I. ; Calvo, Patricia A. ; García-Gómez, Sara ; Guerra-González, Susana; Blanco, Luis
Issue Date28-Mar-2018
PublisherOxford University Press
CitationNucleic Acids Research 46: 4138- 4151 (2018)
AbstractHuman PrimPol is a monomeric enzyme whose DNA primase activity is required to rescue stalled replication forks during nuclear and mitochondrial DNA replication. PrimPol contains an Archeal-Eukaryotic Primases (AEP) core followed by a C-terminal Zn finger-containing domain (ZnFD), that is exclusively required for primer formation and for PrimPol function in vivo. The present study describes the sequential substrate interactions of human PrimPol during primer synthesis, and the relevance of the ZnFD at each individual step. Both the formation of a PrimPol:ssDNA binary complex and the upcoming interaction with the 3-nucleotide (pre-ternary complex) remained intact when lacking the ZnFD. Conversely, the ZnFD was required for the subsequent binding and selection of the 5-nucleotide that will become the first nucleotide of the new primer strand. Providing different 5-site nucleotides, we can conclude that the ZnFD of PrimPol most likely interacts with the - phosphate moiety of the 5-site nucleotide, optimizing formation of the initial dimer. Moreover, the ZnFD also contributes to recognize the cryptic G at the preferred priming sequence 3GTC5. Dimer elongation to obtain long DNA primers occurs processively and is facilitated by the 5-terminal triphosphate, indicating that the ZnFD is also essential in the subsequent translocation/elongation events during DNA primer synthesis.
Identifiersdoi: 10.1093/nar/gky230
issn: 1362-4962
Appears in Collections:(CBM) Artículos
Files in This Item:
File Description SizeFormat 
BlancoL_TheZn-fingerDomain.pdf4,91 MBAdobe PDFThumbnail
Show full item record
Review this work

Related articles:

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.