Polζ ablation in B cells impairs the germinal center reaction, class switch recombination, DNA break repair, and genome stability

Dominik Schenten, Sven Kracker, Gloria Esposito, Sonia Franco, Ulf Klein, Michael Murphy, Frederick W. Alt, Klaus Rajewsky

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Polζ is an error-prone DNA polymerase that is critical for embryonic development and maintenance of genome stability. To analyze its suggested role in somatic hypermutation (SHM) and possible contribution to DNA double-strand break (DSB) repair in class switch recombination (CSR), we ablated Rev3, the catalytic subunit of Polζ, selectively in mature B cells in vivo. The frequency of somatic mutation was reduced in the mutant cells but the pattern of SHM was unaffected. Rev3-deficient B cells also exhibited pronounced chromosomal instability and impaired proliferation capacity. Although the data thus argue against a direct role of Polζ in SHM, Polζ deficiency directly interfered with CSR in that activated Rev3-deficient B cells exhibited a reduced efficiency of CSR and an increased frequency of DNA breaks in the immunoglobulin H locus. Based on our results, we suggest a nonredun- dant role of Polζ in DNA DSB repair through nonhomologous end joining.

Original languageEnglish (US)
Pages (from-to)477-490
Number of pages14
JournalJournal of Experimental Medicine
Volume206
Issue number2
DOIs
StatePublished - Feb 16 2009
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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