title: Orthologous mammalian APOBEC3A cytidine deaminases hypermutate nuclear DNA.
abstract: The human APOBEC3 gene cluster locus encodes polynucleotide cytidine deaminases. Although many act as viral restriction factors through mutation of single-stranded DNA, recent reports have shown that human APOBEC3A was capable of efficiently hypermutating nuclear DNA and inducing DNA breaks in genomic DNA. In addition, the enzyme was unique in efficiently deaminating 5-methylcytidine in single-stranded DNA. To appreciate the evolutionary relevance of these activities, we analyzed A3A-related enzymes from the rhesus and tamarin monkey, horse, sheep, dog, and panda. All proved to be orthologous to the human enzyme in all these activities revealing strong conservation more than 148 My. Hence, their singular role in DNA catabolism is a well-established mechanism probably outweighing any deleterious or pathological roles such as genomic instability and cancer formation.
authors.affiliation: Molecular Retrovirology Unit, Institut Pasteur, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Caval
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Suspène
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vartanian
authors.forename: Simon
authors.initials: S
authors.lastname: Wain-Hobson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003562:Cytidine / Q000031:analogs & derivatives* / Q000378:metabolism; D003564:Cytidine Deaminase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics*; D053903:DNA Breaks, Double-Stranded; D003641:Deamination; D004285:Dogs; D042822:Genomic Instability; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D008322:Mammals / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D011506:Proteins; D003562:Cytidine; D004247:DNA; C121399:APOBEC3A protein, human; D003564:Cytidine Deaminase; C016568:5-methylcytidine
keywords: APOBEC3; cytidine deaminase; double-strand breaks; hypermutation; methylcytidine; nuclear DNA