C-terminal deletion of AID uncouples class switch recombination from somatic hypermutation and gene conversion

Mol Cell. 2003 Aug;12(2):501-8. doi: 10.1016/s1097-2765(03)00309-5.

Abstract

Class-switch recombination (CSR), somatic hypermutation (SHM), and antibody gene conversion are distinct DNA modification reactions, but all are initiated by activation-induced cytidine deaminase (AID), an enzyme that deaminates cytidine residues in single-stranded DNA. Here we describe a mutant form of AID that catalyzes SHM and gene conversion but not CSR. When expressed in E. coli, AID(delta189-198) is more active in catalyzing cytidine deamination than wild-type AID. AID(delta189-198) also promotes high levels of gene conversion and SHM when expressed in eukaryotic cells, but fails to induce CSR. These results underscore an essential role for the C-terminal domain of AID in CSR that is independent of its cytidine deaminase activity and that is not required for either gene conversion or SHM.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Chickens
  • Cytidine Deaminase / chemistry*
  • Cytidine Deaminase / genetics*
  • Escherichia coli / metabolism
  • Flow Cytometry
  • Gene Deletion
  • Green Fluorescent Proteins
  • Humans
  • Immunoglobulin Class Switching*
  • Interleukin-4 / metabolism
  • Luminescent Proteins / metabolism
  • Mice
  • Molecular Sequence Data
  • Mutation*
  • Promoter Regions, Genetic
  • Protein Structure, Tertiary
  • Retroviridae / metabolism
  • Sequence Analysis, DNA
  • Time Factors

Substances

  • Luminescent Proteins
  • Green Fluorescent Proteins
  • Interleukin-4
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase