title: Combinatorial mechanisms regulating AID-dependent DNA deamination: interacting proteins and post-translational modifications.
abstract: Protective humoral immune responses result from immunoglobulin (Ig) diversification reactions that proceed through programmed DNA double-strand breaks and mutations in developing or mature B cells. While primary Ig diversity is dependent on V(D)J recombination and the RAG proteins, secondary diversification is achieved through class switch recombination (CSR) and somatic hypermutation (SHM), which require AID (activation induced deaminase). Because aberrant AID activity can result in mutations in non-Ig loci and DNA translocations between the Ig locus and non-Ig genes, the activity of AID must be stringently regulated. AID mRNA expression is regulated transcriptionally by cytokine stimulation and post-transcriptionally by miRNAs. AID activity is regulated by post-translational modifications, subcellular localization, and interaction with other proteins. All of these molecular mechanisms have evolved to specifically induce AID-dependent mutations and DNA double-strand breaks at the Ig loci to promote maximal Ig gene diversification while limiting the access of this mutator to non-Ig regions.
authors: Immunology Program, Memorial Sloan-Kettering Cancer Center, Gerstner Sloan-Kettering Graduate School, 1275 York Avenue, New York, NY 10065, United States. vuongb@mskcc.org
authors: Bao Q
authors: BQ
authors: Vuong
authors: Jayanta
authors: J
authors: Chaudhuri
mesh_terms: D000818:Animals; D003564:Cytidine Deaminase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D003641:Deamination; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D004247:DNA; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase