Widespread genomic breaks generated by activation-induced cytidine deaminase are prevented by homologous recombination

Nat Immunol. 2010 Sep;11(9):820-6. doi: 10.1038/ni.1909. Epub 2010 Jul 25.


Activation-induced cytidine deaminase (AID) is required for somatic hypermutation and immunoglobulin class switching in activated B cells. Because AID has no known target-site specificity, there have been efforts to identify non-immunoglobulin AID targets. We show here that AID acts promiscuously, generating widespread DNA double-strand breaks (DSBs), genomic instability and cytotoxicity in B cells with less homologous recombination ability. We demonstrate that the homologous-recombination factor XRCC2 suppressed AID-induced off-target DSBs, promoting B cell survival. Finally, we suggest that aberrations that affect human chromosome 7q36, including XRCC2, correlate with genomic instability in B cell cancers. Our findings demonstrate that AID has promiscuous genomic DSB-inducing activity, identify homologous recombination as a safeguard against off-target AID action, and have implications for genomic instability in B cell cancers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / immunology
  • Cell Cycle
  • Cell Survival
  • Cells, Cultured
  • Cytidine Deaminase / metabolism*
  • DNA Breaks*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • Flow Cytometry
  • Genomic Instability
  • Humans
  • Recombination, Genetic / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction


  • DNA-Binding Proteins
  • XRCC2 protein, human
  • Cytidine Deaminase