title: 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.
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.
authors.affiliation: Department of Biological Sciences, University of Southern California, Los Angeles, California 90089-2910, USA.
authors.forename: Phuong
authors.initials: P
authors.lastname: Pham
authors.forename: Peter
authors.initials: P
authors.lastname: Calabrese
authors.forename: Soo Jung
authors.initials: SJ
authors.lastname: Park
authors.forename: Myron F
authors.initials: MF
authors.lastname: Goodman
mesh_terms: D003564:Cytidine Deaminase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003596:Cytosine / Q000737:chemistry* / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003641:Deamination; D004789:Enzyme Activation / Q000502:physiology; D007763:Lac Operon; D016296:Mutagenesis; D014498:Uracil / Q000737:chemistry* / Q000378:metabolism; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D004277:DNA, Single-Stranded; D014498:Uracil; D003596:Cytosine; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase