Recombinogenic phenotype of human activation-induced cytosine deaminase

J Immunol. 2004 Apr 1;172(7):4308-13. doi: 10.4049/jimmunol.172.7.4308.

Abstract

Class switch recombination, gene conversion, and somatic hypermutation that diversify rearranged Ig genes to produce various classes of high affinity Abs are dependent on the enzyme activation-induced cytosine deaminase (AID). Evidence suggests that somatic hypermutation is due to error-prone DNA repair that is initiated by AID-mediated deamination of cytosine in DNA, whereas the mechanism by which AID controls recombination remains to be elucidated. In this study, using a yeast model system, we have observed AID-dependent recombination. Expression of human AID in wild-type yeast is mutagenic for G-C to A-T transitions, and as expected, this mutagenesis is increased upon inactivation of uracil-DNA glycosylase. AID expression also strongly induces intragenic mitotic recombination, but only in a strain possessing uracil-DNA glycosylase. Thus, the initial step of base excision repair is required for AID-dependent recombination and is a branch point for either hypermutagenesis or recombination.

MeSH terms

  • Base Pair Mismatch
  • Cell Line, Tumor
  • Cloning, Molecular
  • Cytidine Deaminase / biosynthesis
  • Cytidine Deaminase / genetics*
  • Cytosine / metabolism
  • DNA Repair
  • Enzyme Induction / immunology
  • Humans
  • Immunoglobulin Class Switching
  • Lymphocyte Activation* / genetics
  • Mutagenesis
  • Phenotype*
  • RNA Editing
  • Recombination, Genetic* / immunology
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics
  • Somatic Hypermutation, Immunoglobulin
  • Two-Hybrid System Techniques

Substances

  • Cytosine
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase