Activation‐Induced Deaminase

Abstract Activation‐induced deaminase is a simple evolutionary tool that nature has utilised to create a very powerful immune system. Hydrolytic deamination is one of the most ancient of enzymatically catalysed reactions, and yet in the context of deoxyribonucleic acid (DNA) can lead to wanted mutations and chromosomal rearrangements in the humoral immune system, changes in the epigenome and inactivation of foreign DNA. While on the dark side, it can lead to oncogenic mutations and translocations across the whole genome and serve as a conduit for nonmutagenic compounds to become mutagenic. Key Concepts AID is the ancestor to APOBEC1, and unlike APOBEC1, AID's enzymatic activity is restricted to DNA. AID does not act on cytidine (the RNA nucleoside); hence, it should be classified as activation‐induced deoxy‐cytosine deaminase, or simply activation‐induced deaminase (AID). AID was the first enzyme discovered to actively induce DNA lesions as part of its physiological function. Nearly 70% of all cancer mutations are derived from the AID/APOBEC family. Environmental factors (e.g. oestrogen) can drive AID expression, allowing for nonmutagenic compounds to elicit oncogenic mutations. AID can be expressed in various tissues and lead to local and global DNA instability. AID's ability to deaminate 5‐methyl cytosine can lead to active DNA demethylation and epigenetic reprogramming. The physiological mutation activity of AID can be harnessed in new tools of biotechnology for in vivo genome editing.