title: AlkB dioxygenase in preventing MMS-induced mutagenesis in Escherichia coli: effect of Pol V and AlkA proteins.
abstract: The deleterious effect of defective alkB allele encoding 1meA/3meC dioxygenase on reactivation of MMS-treated phage DNA has been frequently studied. Here, it is shown that: (i) AlkB protects the cells not only against the genotoxic but also against the potent mutagenic activity of MMS; (ii) mutations arising in alkB-defected strains are umuDC-dependent, and deletion of umuDC dramatically reduce MMS-induced mutations resulting from the presence of 1meA/3meC in DNA; (iii) specificity of MMS-induced argE3-->Arg+ reversions in AB1157 alkB-defective cells are predominantly AT-->TA transversions and GC-->AT transitions; (iv) overproduction of AlkA and the resultant decrease in 3meA residues in DNA dramatically reduce MMS-induced mutations. This reduction is most probably a secondary effect of AlkA due to a decrease in 3meA residues in DNA and, in consequence, suppression of SOS induction and Pol V expression. Overproduction of UmuD'C proteins reverses this effect.
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5A, 02-106 Warszawa, Poland.
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Nieminuszczy
authors.forename: Anna
authors.initials: A
authors.lastname: Sikora
authors.forename: Michał
authors.initials: M
authors.lastname: Wrzesiński
authors.forename: Celina
authors.initials: C
authors.lastname: Janion
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Grzesiuk
mesh_terms: D001120:Arginine / Q000737:chemistry; D003470:Culture Media; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D045647:DNA Glycosylases / Q000378:metabolism; D004252:DNA Mutational Analysis; D004260:DNA Repair; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D008741:Methyl Methanesulfonate / Q000633:toxicity*; D006899:Mixed Function Oxygenases / Q000378:metabolism / Q000502:physiology*; D016296:Mutagenesis; D009153:Mutagens; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D013997:Time Factors
chemical_list: D003470:Culture Media; D029968:Escherichia coli Proteins; D009153:Mutagens; D004247:DNA; D001120:Arginine; D008741:Methyl Methanesulfonate; D006899:Mixed Function Oxygenases; C466427:AlkB protein, E coli; C120926:DNA polymerase V, E coli; D004259:DNA-Directed DNA Polymerase; D045647:DNA Glycosylases; C076131:DNA-3-methyladenine glycosidase II