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CUTTING EDGE |
* National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894; and
Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709
A feature of Ig hypermutation is the presence of hypermutable DNA sequences that are preferentially found in the V regions of Ig genes. Among these, RGYW/WRCY is the most pronounced motif (G:C is a mutable position; R = A/G, Y = C/T, and W = A/T). However, a molecular basis for the high mutability of RGYW was not known until recently. The discovery that activation-induced cytidine deaminase targets the DNA encoding V regions, has enabled the analysis of its targeting properties when expressed outside of the context of hypermutation. We analyzed these data and found evidence that activation-induced cytidine deaminase is the major source of the RGYW mutable motif, but with a new twist: DGYW/WRCH (G:C is the mutable position; D = A/G/T, H = T/C/A) is a better descriptor of the Ig mutation hotspot than RGYW/WRCY. We also found evidence that a DNA repair enzyme may play a role in modifying the sequence of hypermutation hotspots.
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