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 journalArticle

124 Citations (Scopus)

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 1 2006

Fingerprint

proliferating cell nuclear antigen
Ubiquitination
Proliferating Cell Nuclear Antigen
immunoglobulins
Immunoglobulins
DNA-directed DNA polymerase
DNA-Directed DNA Polymerase
ubiquitin
Ubiquitin
Vertebrates
vertebrates
immunoglobulin light chains
Immunoglobulin Light Chains
DNA
lesions (animal)
DNA damage
Yeast
Lysine
DNA Damage
B-lymphocytes

All Science Journal Classification (ASJC) codes

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

Cite this

Arakawa, H., Moldovan, G. L., Saribasak, H., Saribasak, N. N., Jentsch, S., & Buerstedde, J. M. (2006). A role for PCNA ubiquitination in immunoglobulin hypermutation. PLoS biology, 4(11), 1947-1956. https://doi.org/10.1371/journal.pbio.0040366
Arakawa, Hiroshi ; Moldovan, George Lucian ; Saribasak, Huseyin ; Saribasak, Nesibe Nur ; Jentsch, Stefan ; Buerstedde, Jean Marie. / A role for PCNA ubiquitination in immunoglobulin hypermutation. In: PLoS biology. 2006 ; Vol. 4, No. 11. pp. 1947-1956.
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Arakawa, H, Moldovan, GL, Saribasak, H, Saribasak, NN, Jentsch, S & Buerstedde, JM 2006, 'A role for PCNA ubiquitination in immunoglobulin hypermutation', PLoS biology, vol. 4, no. 11, pp. 1947-1956. https://doi.org/10.1371/journal.pbio.0040366

A role for PCNA ubiquitination in immunoglobulin hypermutation. / Arakawa, Hiroshi; Moldovan, George Lucian; Saribasak, Huseyin; Saribasak, Nesibe Nur; Jentsch, Stefan; Buerstedde, Jean Marie.

In: PLoS biology, Vol. 4, No. 11, 01.11.2006, p. 1947-1956.

Research output: Contribution to journalArticle

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Arakawa H, Moldovan GL, Saribasak H, Saribasak NN, Jentsch S, Buerstedde JM. A role for PCNA ubiquitination in immunoglobulin hypermutation. PLoS biology. 2006 Nov 1;4(11):1947-1956. https://doi.org/10.1371/journal.pbio.0040366