%0 Journal Article %1 pham2011analysis %A Pham, P %A Calabrese, P %A Park, S J %A Goodman, M F %D 2011 %J J Biol Chem %K AID B_cells context-dependent-mutation hypermutability mutation_spectrum %N 28 %P 24931-24942 %R 10.1074/jbc.M111.241208 %T 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 %U http://www.ncbi.nlm.nih.gov/pubmed/21572036?dopt=Abstract %V 286 %X 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.

@article{pham2011analysis, 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.}, added-at = {2014-07-02T00:25:33.000+0200}, author = {Pham, P and Calabrese, P and Park, S J and Goodman, M F}, biburl = {https://www.bibsonomy.org/bibtex/252ab716ecf6b08c0cdef36939e47003e/peter.ralph}, doi = {10.1074/jbc.M111.241208}, interhash = {da32f725eb738bc70897554f723ed93b}, intrahash = {52ab716ecf6b08c0cdef36939e47003e}, journal = {J Biol Chem}, keywords = {AID B_cells context-dependent-mutation hypermutability mutation_spectrum}, month = jul, number = 28, pages = {24931-24942}, pmid = {21572036}, timestamp = {2014-07-02T00:32:37.000+0200}, 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}, url = {http://www.ncbi.nlm.nih.gov/pubmed/21572036?dopt=Abstract}, volume = 286, year = 2011 }