Fpg protein protects Escherichia coli K-12 from mutation induction by the carcinogen 4-nitroquinoline 1-oxide.
This paper investigates the role of the fpg gene product in protecting Escherichia coli cells against the lethal and mutagenic effects of 4-nitroquinoline 1-oxide (4NQO). To this end, the araD81 mutation which make the cells sensitive to L-arabinose was combined with an fpg-1::Knr allele, in either an uvrA+ or uvrA-, umuC+ or umuC-, genetic background. Mutation induction was monitored by selecting forward mutations to L-arabinose resistance (Arar). The formamidopyrimidine-DNA glycosylase (Fpg protein) protected bacteria from 4NQO-induced mutagenesis since Fpg- defective cells showed greater Arar mutation induction than fpg+ bacteria did. This was confirmed since the increased sensitivity of the fpg- cells to mutagenesis by 4NQO was suppressed when the Fpg protein was overproduced by placing the fpg gene in a multicopy plasmid vector. The fpg- mutation had no detectable influence on 4NQO mutagenesis in a uvrA- genetic background, but its effect was magnified in umuC- cells. No influence on cell survival was observed after 4NQO treatment. Our data suggest that 8-hydroxyguanine, a non-lethal, non-bulky and directly miscoding lesion, might be responsible for the detected influence of Fpg protein expression on mutation induction by 4NQO. This is in agreement with the reported in vivo formation of 8-hydroxyguanine in cellular DNA after 4NQO exposure. The increased 4NQO-induction of GC to TA transversions on fpg- bacteria further support such a possibility. This work reinforces the role of Fpg protein in the bacterial defense against the mutagenicity by genotoxic agents.
Ruiz-Laguna
J
J
Departamento de Genética, Facultad de Ciencias, Universidad de Cordoba, Spain.
Ariza
R R
RR
Prieto-Alamo
M J
MJ
Boiteux
S
S
Pueyo
C
C
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity*; D001089:Arabinose / Q000633:toxicity; D004351:Drug Resistance; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D009152:Mutagenicity Tests; D009154:Mutation; D009699:N-Glycosyl Hydrolases / Q000378:metabolism / Q000502:physiology*; D010641:Phenotype; D010957:Plasmids / Q000235:genetics
D015112:4-Nitroquinoline-1-oxide; D001089:Arabinose; D009699:N-Glycosyl Hydrolases