DNA polymerase K deficiency does not affect somatic hypermutation in mice

Dominik Schenten, Valerie L. Gerlach, Caixia Guo, Susana Velasco-Miguel, Christa L. Hladik, Charles L. White, Errol C. Friedberg, Klaus Rajewsky, Gloria Esposito

Research output: Contribution to journalReview article

117 Scopus citations

Abstract

Somatic hypermutation (SH) in B cells undergoing T cell-dependent immune responses generates high-affinity antibodies that provide protective immunity. Most current models of SH postulate the introduction of a nick into the DNA and subsequent replication-independent, error-prone short-patch synthesis by one or more DNA polymerases. The PolK (DinB1) gene encodes a specialized mammalian DNA polymerase called DNA polymerase κ (polκ), a member of the recently discovered Y family of DNA polymerases. The mouse PolK gene is expressed at high levels in the seminiferous tubules of the testis and in the adrenal cortex, and at lower levels in most other cells of the body including B lymphocytes. In vitro studies showed that polκ can act as an error-prone polymerase, although they failed to ascribe a clear function to this enzyme. The ability of polκ to generate mutations when extending primers on undamaged DNA templates identifies this enzyme as a potential candidate for the introduction of nucleotide changes in the immunoglobulin (Ig) genes during the process of SH. Here we show that polκ-deficient mice are viable, fertile and able to mount a normal immune response to the antigen (4-hydroxy-3-nitrophenyl)acetyl-chicken γ-globulin (NP-GC). They also mutate their Ig genes normally. However, polκ-deficient embryonic fibroblasts are abnormally sensitive to killing following exposure to ultraviolet (UV) radiation, suggesting a role of polκ in translesion DNA synthesis.

Original languageEnglish (US)
Pages (from-to)3152-3160
Number of pages9
JournalEuropean Journal of Immunology
Volume32
Issue number11
DOIs
StatePublished - Nov 2002

Keywords

  • B cell
  • DNA polymerase K
  • Somatic hypermutation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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