DNA deamination in immunity.
A functional immune system is one of the prerequisites for the survival of a species. Humans have one of the most complicated immune systems, with the ability to learn from and adapt to pathogens. At first, a primary repertoire of antibodies is generated, which, upon antigen encounter, will diversify and adapt to produce a highly specific and potent secondary response, part of which is kept in memory to fight off future infections. In this review, the mechanism as well as the specificities of the key protein in the secondary immune response, activation-induced cytidine deaminase (AID), are highlighted, as well as its role in the DNA deamination model of immunoglobulin diversification. The review also highlights aspects of AID's regulation on both the transcriptional as well as post-translational level and its potential molecular mechanism and specificity. Furthermore, it expands outside the involvement of AID in somatic hypermutation, class switching, and gene conversion to discuss the implications of DNA deamination in epigenetic modifications of DNA (as a potential demethylase), the induction of mutations during oncogenesis, and includes an evolutionary comparison to the DNA deaminase family member APOBEC3G, a key protein in human immunodeficiency virus pathogenesis.
Petersen-Mahrt
Svend
S
DNA Editing Laboratory, Cancer Research UK, Clare Hall Laboratories, South Mimms Hert, UK. skpm@cancer.org.uk
D001402:B-Lymphocytes / Q000378:metabolism; D003564:Cytidine Deaminase / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D003641:Deamination; D044127:Epigenesis, Genetic; D005785:Gene Conversion; D006801:Humans; D017578:Immunoglobulin Class Switching; D009369:Neoplasms / Q000235:genetics / Q000276:immunology; D027041:Somatic Hypermutation, Immunoglobulin; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D004247:DNA; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase