Activation-induced cytidine deaminase (AID), which is both essential and sufficient for forming antibody memory, is also linked to tumorigenesis. AID is found in many B lymphomas, in myeloid leukemia, and in pathogen-induced tumors such as adult T cell leukemia. Although there is no solid evidence that AID causes human tumors, AID-transgenic and AID-deficient mouse models indicate that AID is both sufficient and required for tumorigenesis. Recently, AID's ability to cleave DNA has been shown to depend on topoisomerase 1 (Top1) and a histone H3K4 epigenetic mark. When the level of Top1 protein is decreased by AID activation, it induces irreversible cleavage in highly transcribed targets. This finding and others led to the idea thatthere is an evolutionary link between meiotic recombination and class switch recombination, which share H3K4 trimethyl, topoisomerase, the MRN complex, mismatch repair family proteins, and exonuclease 3. As Top1 has recently beenshown to be involved in many transcription-associated genome instabilities, it is likely that AID took advantage of basic genome instability or diversification to evolve its mechanism for immune diversity. AID targets are therefor