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A role for PCNA ubiquitination in immunoglobulin hypermutation.
PLoS Biol. 4, 1947-1956:e366 (2006)
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
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
Zeitschrift
PLoS Biology
Quellenangaben
Band: 4,
Heft: 11,
Seiten: 1947-1956,
Artikelnummer: e366
Verlag
Public Library of Science (PLoS)
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Molecular Radiation Biology (IMS)