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J Biol Chem. 2011 Jul 15;286(28):24931-42. doi: 10.1074/jbc.M111.241208. Epub 2011 May 12.

Analysis of a single-stranded DNA-scanning process in which activation-induced deoxycytidine deaminase (AID) deaminates C to U haphazardly and inefficiently to ensure mutational diversity.

Author information

1
Department of Biological Sciences, University of Southern California, Los Angeles, California 90089-2910, USA.

Abstract

Enzymes that scan single-stranded (ss) DNA have been studied far less extensively than those that scan double-stranded (ds) DNA. Activation-induced deoxycytidine deaminase (AID) deaminates C to U on single-stranded DNA to initiate immunological diversity. Except for processive deaminations favoring WRC hot motifs (W = (A/T) and R = (G/C)), the rules governing AID scanning remain vague. Here, we examine the patterns of deaminations on naked single-stranded DNA and during transcription of dsDNA by embedding cassettes containing combinations of motifs within a lacZ mutational reporter gene. Deaminations arise randomly, spatially distributed as isolated events and in clusters. The deamination frequency depends on the motif and its surrounding sequence. We propose a random walk model that fits the data well, having a deamination probability of 1-7% per motif encounter. We suggest that inefficient, haphazard deamination produces antibody diversity associated with AID.

PMID:
21572036
PMCID:
PMC3137067
DOI:
10.1074/jbc.M111.241208
[Indexed for MEDLINE]
Free PMC Article

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