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...
