title: Enzymatic methylation of cytosine in DNA is prevented by adjacent O6-methylguanine residues.
abstract: The effect of O6-alkylation of guanine residues on the enzymic methylation of cytosine has been studied using synthetic oligonucleotides in which all guanines in cytosine-guanine sequences at potentially methylatable sites are replaced by O6-methylguanine. In contrast with the unmodified forms, which showed high acceptance activity for methyl-3H-labeled groups from S-adenosyl-L-[methyl-3H]methionine in the presence of DNA methylase, the modified oligonucleotides were not substrates for the enzyme either in the single-stranded or annealed forms. In view of the importance of cytosine methylation in the down-regulation of certain genes, the potential to affect gene expression by this mechanism may be a contributory factor in the toxic and carcinogenic effects of chemical methylating agents.
authors.affiliation: Pharmaceutical Sciences Institute, Aston University, Birmingham, United Kingdom.
authors.forename: P A
authors.initials: PA
authors.lastname: Hepburn
authors.forename: G P
authors.initials: GP
authors.lastname: Margison
authors.forename: M J
authors.initials: MJ
authors.lastname: Tisdale
mesh_terms: D001483:Base Sequence; D003596:Cytosine / Q000378:metabolism*; D004269:DNA, Bacterial / Q000378:metabolism*; D015257:DNA-Cytosine Methylases / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D008745:Methylation; D008837:Micrococcus / Q000378:metabolism; D008969:Molecular Sequence Data
chemical_list: D004269:DNA, Bacterial; D006147:Guanine; D003596:Cytosine; C008449:O-(6)-methylguanine; D015257:DNA-Cytosine Methylases