title: ogt alkyltransferase enhances dibromoalkane mutagenicity in excision repair-deficient Escherichia coli K-12.
abstract: We examined the role of the O6-alkylguanine-DNA alkyltransferase encoded by ogt gene in the sensitivity of Escherichia coli to the mutagenic effects of the dibromoalkanes, dibromoethane and dibromomethane, by comparing responses in ogt- bacteria to those in their isogenic ogt+ parental counterparts. The effects of the uvrABC excision-repair system, the adaptive response, mucAB and umuDC mutagenic processing, and glutathione bioactivation on the differential responses of ogt- and ogt+ bacteria were also studied. Mutation induction was monitored by measuring the frequency of forward mutations to L-arabinose resistance. Induced mutations occurred only in excision repair-defective strains and were totally (with dibromomethane) or substantially (with dibromoethane) dependent on the alkyltransferase (ATase) encoded by the ogt gene. An increased mutagenic response to both dibromoalkanes was also seen in ogt- bacteria that overexpressed the ogt protein from a multicopy plasmid, indicating that the differences in mutability between ogt+ and ogt- bacteria were not dependent on the ogt- null allele carried by the defective strain. The ATase encoded by the constitutive ogt gene was more effective in promoting dibromoalkane mutagenicity than the ada ATase induced by exposure to low doses of a methylating agent. The mutagenicity promoted by the ogt ATase was dependent on both glutathione bioactivation and SOS mutagenic processing. To our knowledge, this paper presents for the first time evidence that DNA ATases, in particular the ATase encoded by the ogt gene, can increase the mutagenic effects of a DNA-damaging agent. The mechanism of this effect has yet to be established.
authors.affiliation: Departamento de Genética, Facultad de Ciencias, Universidad de Córdoba, Espana.
authors.forename: N
authors.initials: N
authors.lastname: Abril
authors.forename: F L
authors.initials: FL
authors.lastname: Luque-Romero
authors.forename: M J
authors.initials: MJ
authors.lastname: Prieto-Alamo
authors.forename: G P
authors.initials: GP
authors.lastname: Margison
authors.forename: C
authors.initials: C
authors.lastname: Pueyo
mesh_terms: D004260:DNA Repair; D004269:DNA, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics*; D015946:Ethylene Dibromide / Q000633:toxicity*; D005978:Glutathione / Q000494:pharmacology; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D008780:Methyltransferases / Q000378:metabolism*; D009152:Mutagenicity Tests; D019853:O(6)-Methylguanine-DNA Methyltransferase; D013014:SOS Response, Genetics
chemical_list: D004269:DNA, Bacterial; D006842:Hydrocarbons, Brominated; D015946:Ethylene Dibromide; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D005978:Glutathione; C027947:methylene bromide