English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/7793
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 | DATACITE
Exportar a otros formatos:

DC FieldValueLanguage
dc.contributor.authorRuiz, José F.-
dc.contributor.authorLucas, Daniel-
dc.contributor.authorGarcía-Palomero, Esther-
dc.contributor.authorSáez, Ana I.-
dc.contributor.authorGonzález, Manuel A.-
dc.contributor.authorPiris, Miguel Ángel-
dc.contributor.authorBernad, Antonio-
dc.contributor.authorBlanco, Luis-
dc.identifier.citationNucleic Acids Research 2004 32(19):5861-5873en_US
dc.description.abstractDNA polymerase µ (Pol µ) is a DNA-dependent DNA polymerase closely related to terminal deoxynucleotidyl transferase (TdT), and prone to induce template/primer misalignments and misincorporation. In addition to a proposed general role in non-homologous end joining of double-strand breaks, its mutagenic potential and preferential expression in secondary lymphoid tissues support a role in somatic hypermutation (SHM) of immunoglobulin genes. Here, we show that human Pol µ protein is expressed in the nucleus of centroblasts obtained from human tonsils, forming a characteristic foci pattern resembling that of other DNA repair proteins in response to DNA damage. Overexpression of human Pol µ in Ramos cells, in which the SHM process is constitutive, augmented the somatic mutations specifically at the variable (V) region of the immunoglobulin genes. The nature of the mutations introduced, mostly base substitutions, supports the contribution of Pol µ to mutation of G and C residues during SHM. In vitro analysis of Pol µ misincorporation on specific templates, that mimic DNA repair intermediates and correspond to mutational hotspots, indicated that many of the mutations observed in vivo can be explained by the capacity of Pol µ to induce transient template/primer misalignmentsen_US
dc.description.sponsorshipThis work was supported by Ministerio de Ciencia y Tecnología Grants BMC 2003-00186 (to L.B.) and BMC 2003-00186 (to A.B.) and by an institutional grant to Centro de Biología Molecular ‘Severo Ochoa’ from Fundación Ramón Areces. The Department of Immunology and Oncology is supported by the Spanish Council for Scientific Research (CSIC) and by Pfizer. J.F.R. was recipient of a fellowship from the Ministerio de Educación y Ciencia. D.L. and E.G.P. were fellows of the Comunidad Autónoma de Madrid.en_US
dc.format.extent987331 bytes-
dc.publisherOxford University Pressen_US
dc.subjectDNA polymerase µen_US
dc.titleOverexpression of human DNA polymerase µ (Pol µ) in a Burkitt's lymphoma cell line affects the somatic hypermutation rateen_US
dc.description.peerreviewedPeer revieweden_US
dc.contributor.funderMinisterio de Ciencia y Tecnología (España)-
dc.contributor.funderFundación Ramón Areces-
dc.contributor.funderConsejo Superior de Investigaciones Científicas (España)-
dc.contributor.funderMinisterio de Educación y Ciencia (España)-
dc.contributor.funderComunidad de Madrid-
Appears in Collections:(CBM) Artículos
Files in This Item:
File Description SizeFormat 
LBlanco_NAR_5861.pdf964,19 kBAdobe PDFThumbnail
Show simple item record

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