Mutator specificity of Escherichia coli alkB117 allele.
The Escherichia coli AlkB protein encoded by alkB gene was recently found to repair cytotoxic DNA lesions 1-methyladenine (1-meA) and 3-methylcytosine (3-meC) by using a novel iron-catalysed oxidative demethylation mechanism that protects the cell from the toxic effects of methylating agents. Mutation in alkB results in increased sensitivity to MMS and elevated level of MMS-induced mutations. The aim of this study was to analyse the mutational specificity of alkB117 in a system developed by J.H. Miller involving two sets of E. coli lacZ mutants, CC101-106 allowing the identification of base pair substitutions, and CC107-CC111 indicating frameshift mutations. Of the six possible base substitutions, the presence of alkB117 allele led to an increased level of GC-->AT transitions and GC-->TA and AT-->TA transversions. After MMS treatment the level of GC-->AT transitions increased the most, 22-fold. Among frameshift mutations, the most numerous were -2CG, -1G, and -1A deletions and +1G insertion. MMS treatment appreciably increased all of the above types of frameshifts, with additional appearance of the +1A insertion.
Nieminuszczy
Jadwiga
J
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warszawa, Poland.
Janion
Celina
C
Grzesiuk
Elzbieta
E
D000483:Alleles; D003062:Codon / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000235:genetics*; D016368:Frameshift Mutation / Q000187:drug effects; D007763:Lac Operon / Q000235:genetics; D008741:Methyl Methanesulfonate / Q000633:toxicity; D006899:Mixed Function Oxygenases / Q000235:genetics*; D016296:Mutagenesis / Q000187:drug effects; D009153:Mutagens / Q000633:toxicity*; D017354:Point Mutation / Q000187:drug effects
D003062:Codon; D029968:Escherichia coli Proteins; D009153:Mutagens; D008741:Methyl Methanesulfonate; D006899:Mixed Function Oxygenases; C466427:AlkB protein, E coli