DNA-cytosine deaminases: from antibody maturation to antiviral defense.
The deamination of cytosines in DNA to uracil, thought to be initiated by free water within the cells, is a well studied pathway by which C to T mutations occur. Until recently, this conversion was frequently referred to as being spontaneous because of the involvement of cellular water. The recent discovery of a family of enzymes in mammalian cells that catalyze this reaction was unexpected and has created excitement in at least two areas of biology, immunology and virology. One of these enzymes, activation-induced cytidine deaminase (AID), is required for the final steps in the maturation of antibodies. The key features of this process include the introduction of a wide variety of base substitutions in the immunoglobulin genes and the creation of region-specific double-strand breaks. Another member of this family, Apobec3G, is involved in the mutational inactivation and degradation of the human immunodeficiency virus (HIV-1). Among the many intriguing features of these processes is the likely involvement of the enzyme that is thought to "protect" cellular DNA against the accumulation of uracils, uracil-DNA glycosylase (UDG). It appears that in certain situations, the newly discovered DNA-cytosine deaminases can team up with UDG to extensively mutate and degrade DNA. This article discusses the many questions raised regarding the role of these enzymes in protecting cells against infections, and about their possible roles in genome evolution and carcinogenesis.
Bhagwat
Ashok S
AS
Department of Chemistry, Wayne State University, 443 Chemistry Building, Detroit, MI 48202-3489, USA. axb@chem.wayne.edu
D003564:Cytidine Deaminase / Q000378:metabolism*; D003596:Cytosine / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004249:DNA Damage; D045647:DNA Glycosylases / Q000378:metabolism; D004260:DNA Repair; D003641:Deamination; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis*; D014498:Uracil / Q000378:metabolism; D051981:Uracil-DNA Glycosidase; D014780:Viruses / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D007074:Immunoglobulin G; D014498:Uracil; D003596:Cytosine; D004247:DNA; D045647:DNA Glycosylases; D051981:Uracil-DNA Glycosidase; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase