DNA adduct 8-hydroxyl-2'-deoxyguanosine (8-hydroxyguanine) affects function of human DNA methyltransferase

8-Hydroxyl-2'-deoxyguanosine (also referred to as 8- hydroxyguanine[8-OH-dG] or 7,8-dihydro-8-oxoguanine), a common DNA adductresulting from injury to DNA via reactive oxygen species, affectsthe in vitro methylation of nearby cytosine moieties by thehuman DNA methyltransferase. The exact position of 8-OH-deoxyguanosinerelative to a CpG dinucleotide appears important to this effect.Our data indicate that 8-OH-deoxyguanosine diminishes the abilityof the methyltransferase to methylate a target cytosine whenthe 8-OH-deoxyguanosine is one or two nucleotides 3' from thecytosine, on the same strand On the other hand 8-OH-deoxyguanosinedoes not diminish the ability of the enzyme to respond to amethyl director (5-methylcytosine) when the 8-OH-deoxyguanosineis on the same strand but one or two nucleotides 3' from themethyl director. Differences in methylation rates as great as13-fold have been detected using various 8-OH-deoxyguanosine-containingoligonucleotides as substrates in methylation assays. Our findingssuggest that oxidative damage of parental strand guanines wouldpermit normal copying of methylation patterns through maintenancemethylation, while oxidative damage of guanines in the nascentstrand DNA would inhibit such methylation.