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A role for PCNA ubiquitination in immunoglobulin hypermutation.

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.

SUBMITTER: Arakawa H

PROVIDER: S-EPMC1618868 | biostudies-literature | 2006 Nov

REPOSITORIES: biostudies-literature

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A role for PCNA ubiquitination in immunoglobulin hypermutation.

Arakawa Hiroshi H Moldovan George-Lucian GL Saribasak Huseyin H Saribasak Nesibe Nur NN Jentsch Stefan S Buerstedde Jean-Marie JM

PLoS biology 20061101 11

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) mu ...[more]

PMID: 17105346

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