DNA Deamination in Antibody Diversity

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Immunoglobulin variable genes undergo several unusual genetic modifications to generate diversity, such as gene rearrangement, gene conversion, somatic hypermutation, and heavy chain class switch recombination. In view of these specialized processes, we examined the possibility that variable genes have intrinsic characteristics that allow them to be processed differently in the course of basic DNA transactions as well. This hypothesis was studied in an experimental system to gauge the relative efficiency of a DNA repair pathway, nucleotide excision repair, on a variable gene and a housekeeping gene. DNA damage was induced by ultraviolet light in murine hybridoma B cells, and repair was measured over time by an alkaline Southern blot technique, which detected removal of cyclobutane pyrimidine dimers. The rate of DNA repair in a rearranged variable gene, VHS107, was compared to that in the dihydrofolate reductase gene. Although both genes were actively transcribed, the VHS107 gene was repaired less efficiently than the dihydrofolate reductase gene. These results suggest that variable genes have inherent properties that affect the efficiency of nucleotide excision repair.