Dimethylsulfate methylation of guanine residues in mammalian DNA: inverse correlation between methylation susceptibility and mutagenesis by bromodeoxyuridine and thymidine.
We have previously demonstrated that mutagenesis by bromodeoxyuridine (BrdU) and thymidine (dT) in mammalian cells occurs with a high degree of sequence specificity within runs of multiple adjacent guanine residues. To determine whether there is a structural component to this sequence specificity, we have analyzed stereochemical properties of guanine residues in different sequence contexts. Stereochemical differences were assessed by measuring the susceptibility of individual guanine residues to methylation by the agent dimethylsulfate (DMS). The results from this study suggest that there is a strong inverse correlation between susceptibility of various guanine residues to DMS methylation and the susceptibility of those residues to mutagenesis by BrdU and dT. These results suggest that the stereochemical attributes of guanine residues in different sequence contexts affect the susceptibility of those guanine residues to mutagenesis by BrdU and dT.
Kresnak
M
M
Department of Genetics, University of Illinois College of Medicine, Chicago 60612.
Davidson
R L
RL
D000818:Animals; D001973:Bromodeoxyuridine / Q000633:toxicity*; D015254:DNA Modification Methylases / Q000378:metabolism; D004252:DNA Mutational Analysis; D015226:Dinucleoside Phosphates / Q000378:metabolism; D005822:Genetic Vectors; D006147:Guanine / Q000737:chemistry / Q000378:metabolism*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008745:Methylation; D051379:Mice; D016296:Mutagenesis; D009153:Mutagens / Q000633:toxicity*; D017354:Point Mutation; D013237:Stereoisomerism; D013463:Sulfuric Acid Esters / Q000378:metabolism; D013936:Thymidine / Q000633:toxicity
D015226:Dinucleoside Phosphates; D009153:Mutagens; D013463:Sulfuric Acid Esters; D006147:Guanine; D015254:DNA Modification Methylases; D007041:Hypoxanthine Phosphoribosyltransferase; D001973:Bromodeoxyuridine; C007482:dimethyl sulfate; D013936:Thymidine