Abstract
A number of observations in the Escherichia coli and Salmonella typhimurium literature could be explained by the hypothesis that a particular purine ribonucleotide precursor can be converted to the corresponding deoxyribonucleotide triphosphate, thereby becoming a base-analogue mutagen. The metabolite in question, AICAR (5-amino-4-carboxamide imidazole riboside 5′-phosphate), is also a by-product of histidine biosynthesis, and its (ribo)triphosphate derivative, ZTP, has been detected in E. coli. We constructed E. coli tester strains that had either a normal AICAR pool (pur + his + strains cultivated without purines or histidine) or no AICAR pool (purF hisG mutant strains, lacking the first enzyme of each pathway and cultivated in the presence of adenine and histidine). Using a set of lacZ mutations, each of which can revert to Lac+ only by a specific substitution mutation, we found that no base substitution event occurs at a higher frequency in the presence of an AICAR pool. We conclude that the normal AICAR pool in E. coli is not a significant source of spontaneous base substitution mutagenesis.
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References
Antón DN (1979) Positive selection of mutants with cell envelope defects of a Salmonella typhimurium strain hypersensitive to the products of genes hisF and hisH. J Bacteriol 137:1271–1281
Bochner BR, Ames BN (1982) ZTP (5-amino 4-imidazole carboxamide riboside 5'−triphosphate): a proposed alarmone for 10-formyl-tetrahydrofolate deficiency. Cell 29:929–937
Cairns J, Foster PL (1991) Adaptive reversion of a frameshift mutation in Escherichia coli. Genetics 128:695–701
Cairns J, Overbaugh J, Miller S (1988) The origin of mutants. Nature 335:142–145
Cupples CG, Miller JH (1988) Effects of amino acid substitutions at the active site in Escherichia coli β-galactosidase. Genetics 120:637–644
Cupples CG, Miller JH (1989) A set of lacZ mutations in Escherichia coli that allow rapid detection of each of the six base substitutions. Proc Natl Acad Sci USA 86:5345–5349
D'Ari R, Huisman O (1983) Novel mechanism of cell division inhibition associated with the SOS response in Escherichia coli. J Bacteriol 156:243–250
Duncan BK, Rockstroh PA, Warner HR (1978) Escherichia coli K-12 mutants deficient in uracil-DNA glycosylase. J Bacteriol 134:1039–1045
Flores A, Fox M, Casadesús J (1993) The pleiotropic effects of Salmonella typhimurium his overexpression do not involve AICAR-induced mutagenesis. Mol Gen Genet 240:360–364
Foster PL (1992) Directed mutation: between unicorns and goats. J Bacteriol 174:1711–1716
Frandsen N, D'Ari R (1993) Excess histidine enzymes cause AICAR-independent filamentation in Escherichia coli. Mol Gen Genet 240:348–354
Geiger JR, Speyer JF (1977) A conditional antimutator in E. coli. Mol Gen Genet 153:87–97
Hall BG (1990) Spontaneous point mutations that occur more often when advantageous than when neutral. Genetics 28:5–16
Hochhauser SJ, Weiss B (1978) Escherichia coli mutants deficient in deoxyuridine triphosphatase. J Bacteriol 134:157–166
Jaffé A, D'Ari R, Norris V (1986) SOS-independent coupling between DNA replication and cell division in Escherichia coli. J Bacteriol 165:66–71
Luria SE, Delbrück M (1943) Mutations of bacteria from virus sensitivity to virus resistance. Genetics 28:491–511
Lyons SM, Speyer JF, Schendel PF (1985) Interaction of an antimutator gene with DNA repair pathways in Escherichia coli K12. Mol Gen Genet 198:336–347
Murray ML, Hartman PE (1972) Overproduction of hisH and hisF gene products leads to inhibition of cell division in Salmonella. Can J Microbiol 18:671–681
Murray V (1987) 5-Amino-4-imidazolecarboxamide is a mutagen in E. coli. Mutat Res 190:89–94
Neuhard J, Nygaard P (1987) Purines and Pyrimidines. In: Neidhardt FC, Ingraham JL, Low KB, Magasanik B, Schaechter M, Umbarger HE (eds) Escherichia coli and Salmonella typhimurium: Cellular and Molecular Biology. American Society for Microbiology, Washington, DC, pp 445–473
Novick A (1956) Mutagens and antimutagens. Brookhaven Symp Biol 8:201–215
Pochet S, D'Ari R (1990) Synthesis and enzymatic polymerisation of 5-amino-l-(2′-deoxy-β-d-ribofuranosyl)imidazole-4-carboxamide-5′-triphosphate. Nucleic Acids Res 18:7127–7131
Rohlman CE, Matthews RG (1990) Role of purine biosynthetic intermediates in response to folate stress in Escherichia coli. J Bacteriol 172:7200–7210
Sabina RL, Holmes EW, Becker MA (1984) The enzymatic synthesis of 5-amino-4-imidazolecarboxamide riboside triphosphate (ZTP). Science 223:1193–1195
Tsui H-CT, Arps PJ, Connolly DM, Winkler ME (1991) Absence of hisT-mediated tRNA pseudouridylation results in a uracil requirement that interferes with Escherichia coli K-12 cell division. J Bacteriol 173:7395–7400
Winkler ME (1987) Biosynthesis of histidine. In: Neidhardt FC, Ingraham JL, Low KB, Magasanik B, Schaechter M, Umbarger HE (eds) Escherichia coli and Salmonella typhimurium: Cellular and Molecular Biology. American Society for Microbiology, Washington, DC, pp 395–411
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Fox, M., Frandsen, N. & D'Ari, R. AICAR is not an endogenous mutagen in Escherichia coli . Molec. Gen. Genet. 240, 355–359 (1993). https://doi.org/10.1007/BF00280386
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DOI: https://doi.org/10.1007/BF00280386