title: Efficient deamination of 5-methylcytidine and 5-substituted cytidine residues in DNA by human APOBEC3A cytidine deaminase.
abstract: Deamination of 5-methylcytidine (5MeC) in DNA results in a G:T mismatch unlike cytidine (C) deamination which gives rise to a G:U pair. Deamination of C was generally considered to arise spontaneously. It is now clear that human APOBEC3A (A3A), a polynucleotide cytidine deaminase (PCD) with specificity for single stranded DNA, can extensively deaminate human nuclear DNA. It is shown here that A3A among all human PCDs can deaminate 5-methylcytidine in a variety of single stranded DNA substrates both in vitro and in transfected cells almost as efficiently as cytidine itself. This ability of A3A to accommodate 5-methyl moiety extends to other small and physiologically relevant substituted cytidine bases such as 5-hydroxy and 5-bromocytidine. As 5MeCpG deamination hotspots characterize many genes associated with cancer it is plausible that A3A is a major player in the onset of cancer.
authors.affiliation: Molecular Retrovirology Unit, Institut Pasteur, Paris, France.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Suspène
authors.forename: Marie-Ming
authors.initials: MM
authors.lastname: Aynaud
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vartanian
authors.forename: Simon
authors.initials: S
authors.lastname: Wain-Hobson
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018899:CpG Islands; D003562:Cytidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D003564:Cytidine Deaminase / Q000737:chemistry* / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000737:chemistry*; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D003641:Deamination; D016158:Genes, p53; D057809:HEK293 Cells; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D011784:Quail; D013379:Substrate Specificity
chemical_list: D004277:DNA, Single-Stranded; D004279:DNA, Viral; D009838:Oligodeoxyribonucleotides; D011506:Proteins; D003562:Cytidine; C121399:APOBEC3A protein, human; D003564:Cytidine Deaminase; C016568:5-methylcytidine