title: A weak adaptive response to alkylation damage in Salmonella typhimurium.
abstract: An efficient adaptive response to alkylation damage was observed in several enterobacterial species, including Klebsiella aerogenes, Shigella sonnei, Shigella boydii, Escherichia alkalescens, Escherichia hermanii, and Escherichia fergusonii. Increased O6-methylguanine-DNA and methylphosphotriester-DNA methyltransferase activities correlated with the induction of a 39-kDa protein recognized by monoclonal antibodies raised against the Escherichia coli Ada protein. Induced methyltransferase activities were similarly observed in Aerobacter aerogenes and Citrobacter intermedius, although no antigenically cross-reacting material was present. Weak induction of a 39-kDa protein immunologically related to the E. coli Ada protein occurred in Salmonella typhimurium. This protein encoded by the cloned S. typhimurium ada gene was shown to be an active methyltransferase which repaired O6-methylguanine and methylphosphotriesters in DNA as efficiently as did the E. coli Ada protein. However, the mehtyltransferase activity of the weakly induced 39-kDa protein in S. typhimurium was not detected, apparently because it was self-methylated and thus inactivated during the adaptive N-methyl-N-nitro-N-nitrosoguanidine pretreatment. In contrast, the E. coli ada gene on a low-copy-number plasmid was efficiently induced in S. typhimurium, and high methyltransferase activities were observed. We concluded that the inefficient induction of the adaptive response in S. typhimurium results from weak transcriptional activation of its ada gene by the self-methylated protein.
authors.affiliation: Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Hertfordshire, United Kingdom.
authors.forename: P
authors.initials: P
authors.lastname: Vaughan
authors.forename: B
authors.initials: B
authors.lastname: Sedgwick
mesh_terms: D000478:Alkylation; D001426:Bacterial Proteins / Q000096:biosynthesis; D004260:DNA Repair; D004269:DNA, Bacterial / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D008770:Methylnitrosourea / Q000633:toxicity*; D008780:Methyltransferases / Q000096:biosynthesis / Q000378:metabolism; D019853:O(6)-Methylguanine-DNA Methyltransferase; D010957:Plasmids; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D014157:Transcription Factors
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D014157:Transcription Factors; D008769:Methylnitronitrosoguanidine; D008770:Methylnitrosourea; D008780:Methyltransferases; C045666:methylphosphotriester methyltransferase; C045675:Ada protein, E coli; D019853:O(6)-Methylguanine-DNA Methyltransferase