Impaired enzymatic methylation of BPDE-modified DNA.
Highly purified DNA methyltransferase from human placenta methylates hemimethylated and 5-methylcytosine-free DNA substrates suggesting that one enzyme molecule may exercise both, the maintenance and de novo activities. Modification of these methyl accepting polymers with (+/-)-r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, anti (BPDE) interferes with the methylation reaction, and this inhibition is proportional to the degree of BPDE-modification. This indicates that BPDE - DNA adducts affect both the maintenance and the de novo DNA methyltransferase activities. The mechanism responsible for such inhibition is related neither to interference of BPDE - DNA adducts with the initial binding of the enzyme to DNA nor with the processive mode of action of the enzyme on the modified DNA template. More likely, the BPDE - DNA adducts inhibit the transmethylation reaction directly at the sites of modification.
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D001580:Benzopyrenes; D001667:Binding, Competitive; D002273:Carcinogens; D004247:DNA; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000032:analysis / Q000494:pharmacology*; D008745:Methylation; D008780:Methyltransferases / Q000494:pharmacology*; D013997:Time Factors
D001580:Benzopyrenes; D002273:Carcinogens; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D004247:DNA; D008780:Methyltransferases; D004248:DNA (Cytosine-5-)-Methyltransferases