title: Reward versus risk: DNA cytidine deaminases triggering immunity and disease.
abstract: The enzymatic deamination of cytosine to uracil, using the free base C, its nucleosides, and nucleotides as substrates, is an essential feature of nucleotide metabolism. However, the deamination of C and, especially, 5 methyl C on DNA is typically detrimental, causing mutations leading to serious human disease. Recently, a family of enzymes has been discovered that catalyzes the conversion of C to U on DNA and RNA, generating favorable mutations that are essential for human survival. Members of the Apobec family of nucleic acid-dependent cytidine deaminases include activation-induced cytidine deaminase (AID) and Apobec3G. AID is required for B cells to undergo somatic hypermutation (SHM) and class switch recombination (CSR), two processes that are needed to produce high-affinity antibodies of all isotypes. Apobec3G is responsible for protection against HIV infection. Recent advances in the biochemical and structural analyses of nucleic acid cytidine deaminases will be discussed in relation to their programmed roles in ensuring antibody diversification and in imposing innate resistance against retroviral infection. The serious negative consequences of expressing Apobec deaminases in the wrong place at the wrong time to catalyze aberrant deamination in "at risk" sequences will be discussed in terms of causing genomic instability and disease.
authors.affiliation: Department of Biological Sciences and Chemistry, University of Southern California, Los Angeles, California 90089-1340, USA.
authors.forename: Phuong
authors.initials: P
authors.lastname: Pham
authors.forename: Ronda
authors.initials: R
authors.lastname: Bransteitter
authors.forename: Myron F
authors.initials: MF
authors.lastname: Goodman
mesh_terms: D003564:Cytidine Deaminase / Q000502:physiology*; D004247:DNA / Q000378:metabolism; D004194:Disease; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate
chemical_list: D004247:DNA; D003564:Cytidine Deaminase