Spontaneous mutagenesis and oxidative damage to DNA in Salmonella typhimurium.
Salmonella typhimurium strains containing deletions of oxyR, a positive regulator of defenses against oxidative stress, show 10- to 55-fold higher frequencies of spontaneous mutagenesis compared to otherwise isogenic oxyR+ control strains. The high spontaneous-mutation frequency in oxyR deletion strains is decreased by a factor of 3 when the strains are grown anaerobically. oxyR deletion strains show an increase in small deletion mutations and at least three of the six possible base-substitution mutations (T.A to A.T, C.G to T.A, and C.G to A.T). However, the largest increase in mutation frequency is observed for T.A to A.T transversions (40- to 146-fold), the base-substitution mutation most frequently caused by chemical oxidants. The introduction into oxyR deletion strains of multicopy plasmids carrying the oxyR-regulated genes for catalase (katG) or alkyl hydroperoxide reductase (ahp) results in overexpression of the respective enzyme activities and decreases the number of spontaneous mutants to wild-type levels. The introduction into oxyR deletions of a plasmid carrying the gene for superoxide dismutase (sodA) decreases the mutation frequency by a factor of 5 in some strain backgrounds. Strains that contain a dominant oxyR mutation and overexpress proteins regulated by oxyR show lower spontaneous-mutation frequencies by a factor of 2. These results indicate that oxyR and oxyR-regulated genes play a significant role in defense against spontaneous oxidative DNA damage. The role of oxidative damage to DNA in "spontaneous" mutagenesis is discussed.
Storz
G
G
Department of Biochemistry, University of California, Berkeley 94720.
Christman
M F
MF
Sies
H
H
Ames
B N
BN
D000693:Anaerobiosis; D002872:Chromosome Deletion; D004249:DNA Damage; D004269:DNA, Bacterial / Q000235:genetics*; D005798:Genes, Bacterial; D005816:Genetic Complementation Test; D009154:Mutation; D010084:Oxidation-Reduction; D010100:Oxygen / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000235:genetics*
D004269:DNA, Bacterial; D010100:Oxygen