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.
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.
Zielenska
M
M
Biology Department, York University, Toronto, Ontario, Canada.
Horsfall
M J
MJ
Glickman
B W
BW
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*
D000477:Alkylating Agents; D009153:Mutagens; D013463:Sulfuric Acid Esters; D013464:Sulfuric Acids; D004247:DNA; C007482:dimethyl sulfate