Uracil residues dependent on the deaminase AID in immunoglobulin gene variable and switch regions

Robert W. Maul, Huseyin Saribasak, Stella A. Martomo, Rhonda L. McClure, William Yang, Alexandra Vaisman, Hillary S. Gramlich, David G. Schatz, Roger Woodgate, David M. Wilson, Patricia J. Gearhart

Research output: Contribution to journalArticlepeer-review

Abstract

Activation-induced deaminase (AID) initiates diversity of immunoglobulin genes through deamination of cytosine to uracil. Two opposing models have been proposed for the deamination of DNA or RNA by AID. Although most data support DNA deamination, there is no physical evidence of uracil residues in immunoglobulin genes. Here we demonstrate their presence by determining the sensitivity of DNA to digestion with uracil DNA glycosylase (UNG) and abasic endonuclease. Using several methods of detection, we identified uracil residues in the variable and switch regions. Uracil residues were generated within 24 h of B cell stimulation, were present on both DNA strands and were found to replace mainly cytosine bases. Our data provide direct evidence for the model that AID functions by deaminating cytosine residues in DNA.

Original languageEnglish (US)
Pages (from-to)70-76
Number of pages7
JournalNature Immunology
Volume12
Issue number1
DOIs
StatePublished - Jan 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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