Molecular biology: Unequal opportunity during class switching

The DNA breakage-and-repair mechanism that generates antibodies of different classes has, in theory, a 50% chance of occurring correctly. But this recombination turns out to be heavily biased towards productive events. See Letter p.134 The process of antibody generation requires rearrangements in the immunoglobulin heavy chain (IgH) locus to juxtapose single V, D and J gene segments, by excising all the remaining segments. In principle, the process making these deletions could also result in inversions. Frederick Alt and colleagues now use high-throughput genome-wide sequencing to examine the long-standing question of why the process at this locus has a directional bias towards deletion rather than inversion. They find that it involves sequences within the IgH locus itself, double-strand DNA breaks initiated by the AID deaminase, and double-strand break repair factors 53BP1 and ATM.