A role for PCNA ubiquitination in immunoglobulin hypermutation.
PLoS Biol
; 4(11): e366, 2006 Nov.
Article
em En
| MEDLINE
| ID: mdl-17105346
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.
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Base de dados:
MEDLINE
Assunto principal:
Cadeias lambda de Imunoglobulina
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Antígeno Nuclear de Célula em Proliferação
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Ubiquitina
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Mutação
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article