Summary
Treatment of diploid yeast cultures with the amino acid analogue, para-fluorophenylalanine (PFPA), at concentrations which caused inhibition of growth, resulted in up to 5 fold increases in the frequency of mitotic gene conversion at two different heteroallelic loci. With haploid yeast cultures, growth in PFPA increased the rate of forward mutation to canavanine resistance by at least 2 fold.
Growth of diploids in PFPA prior to exposure to the deaminating agent nitrous acid, the cross-linking agent mitomycin C, the alkylating chemical ethylmethanesulphonate (EMS) and UV light resulted in significant changes in the potency of these diverse mutagens to induce intragenic recombination. For all four mutagens, increased frequencies of gene convertants/viable cell were observed in those cultures which had been exposed to the amino acid analogue prior to mutagen treatment. In haploid WT yeast cells, amino acid analogue incorporation resulted in an enhanced frequency of UV induced forward mutation to canavanine resistance whilst in a DNA repair deficient rad 6 mutant this interaction between UV and PFPA was abolished.
The results have been interpreted on the basis of incorporation of the analogue into enzymes involved with DNA replication with a consequent loss of fidelity of such enzymes and increased errors in base incorporation.
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References
Cox, B.S., Parry, J.M.: The isolation, genetics and survival characteristics of ultraviolet light sensitive mutants in yeast. Mutation Res. 6, 37–55 (1968)
Davies, P.J., Evans, W.E., Parry, J.M.: Mitotic recombination induced by chemical and physical agents in the yeast, Saccharomyces cerevisiae. Mutation Res. 29, 301–314 (1975)
Davies, P.J., Parry, J.M.: The induction of mitotic gene conversion by chemical and physical mutagens as a function of culture age in the yeast, Saccharomyces cerevisiae. Molec. gen. Genet. 148, 165–170 (1976)
Drake, J.W., Baltz, R.H.: The biochemistry of mutagenesis. Ann. Rev. Biochem. 45, 11–37 (1976)
Freifelder, D.: Lethal changes in bacteriophage DNA produced by X-rays. Radiation Res. 6, 80–96 Suppl. (1966)
Game, J.C., Cox, B.S.: Allelism tests of mutants affecting sensitivity to radiation in yeast: A proposed nomenclature. Mutation Res. 12, 328–331 (1971)
Hare, J.D.: Nuclear alterations in mammalian cells induced by L-canavanine. J. Cell. Physiol. 75, 129–131 (1970)
Holliday, R.: Biochemical measure of the time and frequency of radiation induced allelic recombination in Ustilago maydis. Nature (Lond.) New Biol. 232, 233–236 (1971)
Johnson, A.W.B.: Effects of p-flurophenylalanine on the induction of mutations in bacteriophage T4. II Nitrous acid mutagenesis. Mutation Res. 27, 17–26 (1975)
Langridge, J.: Genetic and enzymatic experiments relating to the tertiary structure of β-galactosidase. J. Bact. 96, 1711–1717 (1968)
Lawrence, C.W., Christenson, R.: UV mutagenesis in radiation sensitive strains of yeast. Genetics 82, 207–232 (1976)
Lemontt, J.F.: Pathways of ultraviolet mutability in Saccharomyces cerevisiae. III Genetic analysis and properties of mutants resistant to ultraviolet induced forward mutation. Mutation Res. 43, 171–204 (1977)
Lewis, C.M., Tarrant, G.M.: Induction of mutation by 5-Fluorouracil and amino acid analogues in Ustilago maydis. Mutation Res. 12 349–356 (1971)
Lhoas, P.: Mitotic haploidization by treatment of Aspergillus niger diploids with para-fluorophenyl-alanine. Nature (Lond.) 190, 744 (1960)
McBride, A.C., Gowans, C.S.: The induction of gene mutation and chromosome aberrations in Chlamydomonas by a phenylalanine analogue, 2-amino-3-phenyl butanoic acid. Genet. Res. 14, 121–127 (1969)
Sedgwick, S.G.: Misrepair of overlapping daughter strand gaps as a possible mechanism for UV induced mutagenesis in UVR strains of Escherichia coli: A general model for induced mutagenesis by repair (SOS repair) of closely spaced DNA lesions. Mutation Res. 41, 185–200 (1976)
Springgate, C., Loeb, L.A.: Mutagenic DNA polymerases in human leukaemic cells. Proc. nat. Acad. Sci. (Wash.) 70, 245–249 (1973)
Stomnaes, O.: Genetic changes in Saccharomyces cerevisiae grown on medium containing DL-para-fluorophenylalanine. Hereditas 59, 197–220 (1968)
Talmud, P.J.: Mutational synergism between p-fluorophenylalanine and UV in Coprinus lagopus. Mutation Res. 43, 213–222 (1977)
Talmud, P.J., Lewis, D.: The mutagenicity of amino acid analogues in Coprinus lagopus. Genet. Res. 23, 47–61 (1974a)
Talmud, P.J., Lewis, D.: Mutagenicity of amino acid analogues in eukaryotes. Nature (Lond.) 249, 563–564 (1974b)
Wildenberg, J., Meselson, M.: Mismatch repair in heteroduplex DNA. Proc. nat. Acad. Sci. (Wash.) 72, 2202–2206 (1975)
Witkin, E.M.: Ultraviolet mutagenesis and inducible DNA repair in Escherichia coli. Bact. Rev. 40, 869–907 (1976)
Zimmermann, F.K.: Induction of mitotic gene conversion by mutagens. Mutation Res. 11, 327–337 (1971)
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Davies, P.J., Parry, J.M. The modification of induced genetic change in yeast by an amino acid analogue. Molec. Gen. Genet. 162, 183–190 (1978). https://doi.org/10.1007/BF00267875
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DOI: https://doi.org/10.1007/BF00267875