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PLoS Biol. 2006 Nov;4(11):e366.

A role for PCNA ubiquitination in immunoglobulin hypermutation.

Author information

  • 1Gesellschaft für Strahlen Forschung, Institute for Molecular Radiobiology, Neuherberg-Munich, Germany.

Abstract

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.

Comment in

PMID:
17105346
[PubMed - indexed for MEDLINE]
PMCID:
PMC1618868
Free PMC Article

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