A dangerously mutagenic protein is targeted to a single genomic site by ssDNA, report Ronai et al. (page 181).

High frequency mutation at the immunoglobulin V region improves antibody affinity and specificity as part of the adaptive immune response. AID (activation-induced cytidine deaminase), which converts deoxycytidines to deoxyuridines, initiates this mutation process. These conversions then induce various error-prone repair mechanisms, increasing the mutation rate further.

AID must be targeted carefully, however, as it is a potent mutagen. Indeed mistargeting of AID-induced mutations is thought to cause B cell lymphomas.

AID's only in vitro substrate is ssDNA. The team isolated chromatin from B cells undergoing somatic hypermutation (SHM) and found that chromatin- and transcription-dependent ssDNA was present at V regions.

Many genes in B cells are highly transcribed, but the team found that such loci had much less ssDNA than those undergoing SHM. The ssDNA may be short lived during normal transcription but persist at V regions, perhaps due to RNA pol II pausing. Whatever the reason, it seems that the specific abundance of ssDNA at the V region might be one of the chromatin signals for targeting AID.