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Nat Immunol. 2011 Jan;12(1):70-6. doi: 10.1038/ni.1970. Epub 2010 Dec 12.

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

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1
Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.

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.

PMID:
21151102
PMCID:
PMC3653439
DOI:
10.1038/ni.1970
[Indexed for MEDLINE]
Free PMC Article
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