Deamination at a methylcytosine within a CpG creates a T:G mismatch which persists due to catalytic inefficiency of methyl-CpG binding domain protein 4 (MBD4) and thymine DNA glycosylase (TDG) in cleaving the thymine glycosidic bond, leaving an abasic site (asterisk). Single-strand breaks are generated either by the normal base excision repair pathway of glycosylase and AP endonuclease (APE) activity, or by RAG nicking the mismatch directly, resulting in a poorly-ligatable flap. Heterogeneous RAG nicking of the remaining strand creates a double-strand break close to the original site of the T:G mismatch. We observe the following features at CpG-type translocation hotspots: (1) an extremely high degree of focusing to CpGs, (2) a breakpoint distribution consistent with a structure-specific endonuclease, (3) specificity to the pro-B/pre-B stage, and (4) specificity to the B-cell lineage. Involvement of the RAG complex explains points 2 and 3, while involvement of AID explains point 4 and is strongly suggestive for point 1.