AID overwhelms Polβ in class-switching B cells

The machinery that repairs spontaneous DNA mutations fails when the mutations are purposely induced by an enzyme in activated B cells. Wu and Stavnezer (page 1677) now find that the enzyme wins because it induces too much damage for repair proteins to keep up with.

The spontaneous mutation of cytosine bases to uracils is corrected by a process that removes the wrong bases, cuts the DNA at the empty spots, and reinserts the correct bases. This normally efficient process fails in B cells that are switching from producing IgM to making other classes of antibodies. In these cells, cytosines are converted to uracils by the enzyme activation-induced deaminase (AID). The mutated DNA is cut normally, but the ends then recombine to produce new types of antibodies. Recombination thus occurs at the...