Hypersensitivity of Escherichia coli Delta(uvrB-bio) mutants to 6-hydroxylaminopurine and other base analogs is due to a defect in molybdenum cofactor biosynthesis.
We have shown previously that Escherichia coli and Salmonella enterica serovar Typhimurium strains carrying a deletion of the uvrB-bio region are hypersensitive to the mutagenic and toxic action of 6-hydroxylaminopurine (HAP) and related base analogs. This sensitivity is not due to the uvrB excision repair defect associated with this deletion because a uvrB point mutation or a uvrA deficiency does not cause hypersensitivity. In the present work, we have investigated which gene(s) within the deleted region may be responsible for this effect. Using independent approaches, we isolated both a point mutation and a transposon insertion in the moeA gene, which is located in the region covered by the deletion, that conferred HAP sensitivity equal to that conferred by the uvrB-bio deletion. The moeAB operon provides one of a large number of genes responsible for biosynthesis of the molybdenum cofactor. Defects in other genes in the same pathway, such as moa or mod, also lead to the same HAP-hypersensitive phenotype. We propose that the molybdenum cofactor is required as a cofactor for an as yet unidentified enzyme (or enzymes) that acts to inactivate HAP and other related compounds.
Kozmin
S G
SG
Department of Genetics, Sankt-Petersburg State University, Saint Petersburg, Russia.
Pavlov
Y I
YI
Dunn
R L
RL
Schaaper
R M
RM
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D003067:Coenzymes; D004265:DNA Helicases; D004251:DNA Transposable Elements; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development; D029968:Escherichia coli Proteins; D017353:Gene Deletion; D008667:Metalloproteins / Q000378:metabolism*; D008982:Molybdenum / Q000378:metabolism*; D000090006:Molybdenum Cofactors; D009876:Operon; D017354:Point Mutation; D011621:Pteridines / Q000378:metabolism*; D013466:Sulfurtransferases / Q000235:genetics / Q000378:metabolism
D000225:Adenine; D001426:Bacterial Proteins; D003067:Coenzymes; D004265:DNA Helicases; D004251:DNA Transposable Elements; D029968:Escherichia coli Proteins; D008667:Metalloproteins; D008982:Molybdenum; D000090006:Molybdenum Cofactors; D011621:Pteridines; D013466:Sulfurtransferases; C058093:UvrB protein, E coli; C032610:6-N-hydroxylaminopurine; C022261:molybdopterin; C111302:MoeA protein, E coli