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

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.

SUBMITTER: Maul RW

PROVIDER: S-EPMC3653439 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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

Maul Robert W RW Saribasak Huseyin H Martomo Stella A SA McClure Rhonda L RL Yang William W Vaisman Alexandra A Gramlich Hillary S HS Schatz David G DG Woodgate Roger R Wilson David M DM Gearhart Patricia J PJ

Nature immunology 20101212 1

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 ...[more]

PMID: 21151102

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