STEPS ALONG THE PATHWAY OF V(D)J RECOMBINATION

The mechanism of lymphoid-specific gene rearrangement (V(D)J recombination) is discussed, with a focus on the existence of broken DNA intermediates. Older evidence in support of this idea includes the sequence alterations at the recombined junctions and the presence of aberrant recombinants. More recently, broken DNA molecules have been directly detected in recombinationally active cells. The signal sequence ends have normal blunt-ended DNA breaks, but the coding ends have a hairpin (self-joined) structure that provides an explanation for the self-complementary P nucleotide insertions often found after V(D)J joining in the antigen receptor genes.