AID and partners: for better and (not) for worse

Post-rearrangement diversification of the antibody repertoire relies on a DNA editing factor, the cytidine deaminase AID. How B lymphocytes avoid generalized mutagenesis while expressing high levels of AID remained a long-standing question. Genome-wide studies of AID targeting combined to the discovery of several co-factors controlling its recruitment and its local activity shed new light on this enigma.

► Large scale sequencing shows that AID binds and deaminates thousands of loci.
► AID is recruited to its targets by RNA Pol II stalling, via its interaction with Spt5.
► Interaction with the RNA exosome licenses AID access to the transcribed strand.
► Off-targeting produces DNA breaks at various loci, even in non-transcribed regions.