title: The dissimilar mutational consequences of SN1 and SN2 DNA alkylation pathways: clues from the mutational specificity of dimethylsulphate in the lacI gene of Escherichia coli.
abstract: The mutational specificity of the monofunctional alkylating agent dimethylsulphate has been determined through the DNA sequence characterization of 121 lacI-d mutations of Escherichia coli. The predominant mutation induced was the G:C----A:T transition (75%). Transversions constituted 20% of all mutation with the greatest contribution being that of G:C----T:A events (12%). Runs of G:C base pairs were the preferred sites of frameshift mutation. One 6-bp sequence (5'-CCCGCG-3') appeared to be highly susceptible to all classes of mutation and events within this sequence accounted for 33% of all mutations characterized. Although the distribution of G:C----A:T mutations appeared non-random, the site-specificity observed was quite different from that reported for SN1 alkylating agents. The results of this study highlight the differences between the consequences of SN1 and SN2 alkylation pathways.
authors.affiliation: Biology Department, York University, Toronto, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Zielenska
authors.forename: M J
authors.initials: MJ
authors.lastname: Horsfall
authors.forename: B W
authors.initials: BW
authors.lastname: Glickman
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity*; D001483:Base Sequence; D004247:DNA / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D005798:Genes, Bacterial / Q000187:drug effects*; D008969:Molecular Sequence Data; D009153:Mutagens; D013463:Sulfuric Acid Esters / Q000633:toxicity*; D013464:Sulfuric Acids / Q000633:toxicity*
chemical_list: D000477:Alkylating Agents; D009153:Mutagens; D013463:Sulfuric Acid Esters; D013464:Sulfuric Acids; D004247:DNA; C007482:dimethyl sulfate