A role for PCNA ubiquitination in immunoglobulin hypermutation

Hiroshi Arakawa, George Lucian Moldovan, Huseyin Saribasak, Nesibe Nur Saribasak, Stefan Jentsch, Jean Marie Buerstedde

Research output: Contribution to journalArticlepeer-review

126 Scopus citations

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 PCNAK164R 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.

Original languageEnglish (US)
Pages (from-to)1947-1956
Number of pages10
JournalPLoS biology
Volume4
Issue number11
DOIs
StatePublished - Nov 2006

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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