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Arakawa, H. ; Moldovan, G.-L.* ; Saribasak, H.* ; Saribasak, N.N. ; Jentsch, S.* ; Buerstedde, J.-M.

A role for PCNA ubiquitination in immunoglobulin hypermutation.

PLoS Biol. 4, 1947-1956:e366 (2006)
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Proliferating cell nuclear antigen ( PCNA) is a DNA polymerase cofactor and regulator of replication-linked functions. Upon DNA damage, yeast and vertebrate PCNA is modified at the conserved lysine K164 by ubiquitin, which mediates error-prone replication across lesions via translesion polymerases. We investigated the role of PCNA ubiquitination in variants of the DT40 B cell line that are mutant in K164 of PCNA or in Rad18, which is involved in PCNA ubiquitination. Remarkably, the PCNA(K164R) mutation not only renders cells sensitive to DNA-damaging agents, but also strongly reduces activation induced deaminase-dependent single-nucleotide substitutions in the immunoglobulin light-chain locus. This is the first evidence, to our knowledge, that vertebrates exploit the PCNA-ubiquitin pathway for immunoglobulin hypermutation, most likely through the recruitment of error-prone DNA polymerases.
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Publication type Article: Journal article
Document type Scientific Article
Keywords DNA-POLYMERASE-ETA; GENE CONVERSION; SOMATIC HYPERMUTATION; DAMAGE TOLERANCE; DEAMINASE AID; CELL-LINE; REV1; SUMO; DT40; MUTATION
ISSN (print) / ISBN 1544-9173
e-ISSN 1545-7885
Journal PLoS Biology
Quellenangaben Volume: 4, Issue: 11, Pages: 1947-1956, Article Number: e366 Supplement: ,
Publisher Public Library of Science (PLoS)
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Radiation Biology (IMS)