English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/123805
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:


DNA expansions generated by human Polm on iterative sequences

AuthorsAza, Ana ; Martín, María José ; Juárez, Raquel; Blanco, Luis ; Terrados, Gloria
Issue Date7-Jan-2013
PublisherOxford University Press
CitationNucleic Acids Research 41: 253- 263 (2013)
AbstractPolm is the only DNA polymerase equipped with template-directed and terminal transferase activities. Polm is also able to accept distortions in both primer and template strands, resulting in misinsertions and extension of realigned mismatched primer terminus. In this study, we propose a model for human Polm-mediated dinucleotide expansion as a function of the sequence context. In this model, Polm requires an initial dislocation, that must be subsequently stabilized, to generate large sequence expansions at different 5′-P-containing DNA substrates, including those that mimic non-homologous end-joining (NHEJ) intermediates. Our mechanistic studies point at human Polm residues His329 and Arg387 as responsible for regulating nucleotide expansions occurring during DNA repair transactions, either promoting or blocking, respectively, iterative polymerization. This is reminiscent of the role of both residues in the mechanism of terminal transferase activity. The iterative synthesis performed by Polο at various contexts may lead to frameshift mutations producing DNA damage and instability, which may end in different human disorders, including cancer or congenital abnormalities.
Identifiersdoi: 10.1093/nar/gks1054
issn: 0305-1048
Appears in Collections:(CBM) Artículos
Files in This Item:
File Description SizeFormat 
Luis_Blanco_DNA_expansions.pdf5,52 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.