The limitations of genomic information forced our ancestors to adopt a strategy for introducing somatic DNA alterations with the risk of genome instability. Although activation-induced deaminase (AID) is involved in DNA cleavage in somatic hypermutation and class-switch recombination, its mechanism of action has been debated extensively, with the two main hypotheses being distinguished by the chief target of AID: RNA or DNA. The principle distinction between the two hypotheses is the requirement for translation of edited mRNA or uracil removal from DNA for DNA cleavage. Although a series of experiments has provided support for the 'RNA-editing' hypothesis and requires reevaluation of the 'DNA-deamination' hypothesis, definitive proof is yet to come.
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