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Mutation as an error in base pairing

I. The mutagenicity of base analogues and their incorporation into the DNA ofSalmonella typhimurium

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Summary

Reversion patterns of twenty-three mutants at two tryptophan loci (try C andD) inSalmonella typhimurium have been investigated after treatment with three specific mutagens. The compounds used were the base analogues, 5-bromouracil (BU) and 2-aminopurine (AP), and nitrous acid. The mutant alleles showed considerable specificity of response to the mutagens. The increased frequency of mutants after growth in the presence of base analogues was not due to selection of pre-existing mutants as shown by reconstruction experiments. It was determined that BU can be incorporated into the DNA of this organism by replacing thymine. A small amount of unaltered AP was recovered from the DNA of a purine-requiring mutant. These findings suggest that BU and AP induce “basepair transitons” inSalmonella typhimurium as had been previously observed for bacteriophage (Freese 1959).

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References

  • Balbinder, E.: Genetic studies of thetryC andtryD loci inSalmonella typhimurium. (In press, 1961.)

  • Bautz, E., andE. Freese: On the mutagenic effect of alkylating agents. Proc. nat. Acad. Sci. (Wash.)46, 1585–1594 (1960).

    Google Scholar 

  • Benzer, S.: The elementary units of heredity. InW. D. McElroy andB. Glass (edit.). The chemical basis of heredity, p. 50–93. Baltimore: The Johns Hopkins Press 1957.

    Google Scholar 

  • Bessman, M. J., I. R. Lehman, J. Adler, E. Zimmerman andA. Kornberg: Enzymatic synthesis of deoxyribonucleic acid. III. The incorporation of pyrimidine and puring analogues into deoxyribonucleic acid. Proc. nat. Acad. Sci. (Wash.)44, 633–640 (1958).

    Google Scholar 

  • Brenner, S., andJ. D. Smith: Induction of mutation in the deoxyribonucleic acid of phage T2 synthesized in the presence of chloramphenicol. Virology8, 124–125 (1959).

    Google Scholar 

  • Chargaff, E.: Isolation and composition of the deoxypentose nucleic acids and the corresponding nucleoproteins. InE. Chargaff andJ. N. Davidson (edit.). The nucleic acids, vol. I, p. 307–368. New York: Academic Press 1955.

    Google Scholar 

  • —,R. Lipshitz, C. Green andM. E. Hodes: The composition of the deoxyribonucleic acid of Salmon sperm. J. biol. Chem.192, 223–230 (1951).

    Google Scholar 

  • Cohen, S. S., andH. D. Barner: Studies on the induction of thymine deficiency and on the effects of thymine and thymidine analogues inEscherichia coli. J. Bact.71, 588–597 (1956).

    Google Scholar 

  • —,J. G. Flaks, H. D. Barner, M. R. Loeb andJ. Lichtenstein: The mode of action of 5-fluorouracil and its derivatives. Proc. Nat. Acad. Sci. (Wash.)44, 1004–1012 (1958).

    Google Scholar 

  • Demerec, M., andP. E. Hartman: Complex loci in microorganisms. Ann. Rev. Microbiol.13, 377–400 (1959).

    Google Scholar 

  • Dische, Z.: Color reactions of nucleic acid components. InE. Chargaff andJ. N. Davidson (edit.). The nucleic acids, vol. I, p. 285–305. New York: Academic Press 1955.

    Google Scholar 

  • Doudney, C. O., andF. L. Haas: Mutation induction and macromolecular synthesis in bacteria. Proc. nat. Acad. Sci. (Wash.)45, 709–722 (1959).

    Google Scholar 

  • Dunn, D. B., andJ. D. Smith: Effects of 5-halogenated uracils on the growth ofEscherichia coli and their incorporation into deoxynucleic acids. Biochem. J.67, 494–506 (1957).

    Google Scholar 

  • ——: The occurrence of 6-methylaminopurine in deoxyribonucleic acids. Biochem. J.68, 627–636 (1958).

    Google Scholar 

  • ——: Occurrence of a new base in the deoxynucleic acid of a strain ofBacterium coli. Nature (Lond.)175, 336–337 (1955).

    Google Scholar 

  • Edmonds, M.: Deoxyriboside synthesis by Ehrlich ascites cells. Fed. Proc.17, 215 (1958).

    Google Scholar 

  • Freese, E.: The difference between spontaneous and base-analogue induced mutations of phage T4. Proc. nat. Acad. Sci. (Wash.)45, 622–633 (1959a).

    Google Scholar 

  • —: The specific mutagenic effect of base analogues on phage T4. J. Mol. Biol.1, 87–105 (1959b).

    Google Scholar 

  • —: On the molecular explanation of spontaneous and induced mutations. In Structure and function of genetic elements. Brookhaven Symposia in Biology12, 63–75 (1959c).

    Google Scholar 

  • Friedkin, M., andA. Kornberg: The enzymatic conversion of deoxyuridylic acid to thymidylic acid and the participation of tetrahydrofolic acid. InW. D. McElroy andB. Glass (edit.). The chemical basis of heredity, p. 609–614. Baltimore: Johns Hopkins Press 1957.

    Google Scholar 

  • Glass, E. A., andA. Novick: Induction of mutation in chloramphenicol-inhibited bacteria. J. Bact.77, 10–16 (1959).

    Google Scholar 

  • Greer, S.: Studies on ultraviolet irradiation ofEscherichia coli containing 5-bromouracil in its DNA. J. gen. Microbiol.22, 618–634 (1960).

    Google Scholar 

  • — andS. Zamenhof: Loss of purines from DNA heated in mutagenic condition at physiological pH. Fed. Proc.18, 238 (1959).

    Google Scholar 

  • Heidelberger, C., N. K. Chaudhuri, P. Danneberg, D. Mooren, L. Griesbach, R. Duschinsky, R. J. Schnitzer, E. Pleven andY. Scheiner: Fluorinated pyrimidines, a new class of tumour-inhibitory compounds. Nature (Lond.)179, 663–666 (1957).

    Google Scholar 

  • Hurst, R. O., andG. C. Butler: The chromatographic separation of phosphatases in snake venoms. J. biol. Chem.193, 91–96 (1951).

    Google Scholar 

  • Iyer, V. N., andW. Szibalski: Two simple methods for the delection of chemical mutagens. Appl. Microbiol.6, 23–29 (1958).

    Google Scholar 

  • Kaudewitz, F.: Inaktivierende und mutagene Wirkung salpetriger Säure auf Zellen vonEscherichia coli. Z. Naturforsch.146, 528–537 (1959).

    Google Scholar 

  • Khorona, H. G., J. F. Fernandes andA. Kornberg: Pyrophosphoryl of ribose 5-phosphate in the enzymatic synthesis of 5-phosphorylribose 1-pyrophosphate. J. biol. Chem.230, 941–948 (1958).

    Google Scholar 

  • Kirchner, C. E. J.: The effect of mutator gene on molecular changes and mutations inSalmonella typhimurium. J. Mol. Biol.2, 331–338 (1960).

    Google Scholar 

  • Lawley, P. D.: The relative reactivities of deoxyribonucleotides and of the bases of DNA towards alkylating agents. Biochim. biophys. Acta26, 450–451 (1957).

    Google Scholar 

  • Litman, R. M., andH. Ephrussi-Taylor: Inactuation et mutation des facteurs genetiques de l'acide deoxyribonucleique dupneumocoque par l'ultraviolet et par l'acide nitreux. C.R. Acad. Sci. (Paris)249, 838–840 (1959).

    Google Scholar 

  • —, andA. B. Pardee: Production of bacteriophage mutants by a disturbance of deoxyribonucleic acid metabolism. Nature (Lond.)178, 529–531 (1956).

    Google Scholar 

  • ——: Mutations of bacteriophage T2 induced by bromouracil in the presence of chloramphenicol. Virology8, 125–127 (1959).

    Google Scholar 

  • ——: The induction of mutants of bacteriophage T2 by 5-bromouracil. III. Nutritional and structural evidence regarding mutagenic action. Biochim. biophys. Acta42, 117–130 (1960a).

    Google Scholar 

  • ——: The induction of mutants of bacteriophage T2 by 5-bromouracil. IV. Kinetics of bromouracil-induced mutagenesis. Biochim. biophys. Acta42, 131–140 (1960b).

    Google Scholar 

  • Lorkiewicz, Z., andW. Szybalski: Genetic effects of halogenated thymidine analogs incorporated during thymidylate synthetase inhibition. Biochem. Biophys. Res. Comm.2, 413–418 (1960).

    Google Scholar 

  • Loveless, A.: The influence of radiomimetic substances on deoxyribonucleic acid synthesis and function studied inEscherichia coli phage systems. III. Mutation of T2 bacteriophage as a consequence of alkylation in vitro: the uniqueness of ethylation. Proc. roy. Soc. B150, 497–508 (1959).

    Google Scholar 

  • Magasanik, B., A. K. Magasanik andF. C. Neidhardt: Regulation of growth and composition of the bacterial cell. InG. E. W. Wolsten-Holine andC. M. O'Conner, edit. Regulation of cell metabolism. Ciba Foundation Symposium 1959.

  • E. Vischer, R. Doniger, D. Elson andE. Chargaff: The separation and estimation of ribonucleotides in minute quantities. J. biol. Chem.186, 37–50 (1950).

    Google Scholar 

  • Markham, R., andJ. D. Smith: Chromatographic studies of nucleic acid. I. A technique for the identification and estimation of purine and pyrimidine bases, nucleosides and related substances. Biochem. J.45, 294–298 (1949).

    Google Scholar 

  • Matthews, R. E. F.: The incorporation of 8-azaguanine into nucleic acid of tobacco mosaic virus. Nature (Lond.)171, 1065–1066 (1953).

    Google Scholar 

  • Miyake, T.: Mutator factor inSalmonella typhimurium. Genetics45, 11–14 (1960).

    Google Scholar 

  • Mundry, K. W., andA. Gierer: Die Erzeugung von Mutationen des Tabakmosaikvirus durch chemische Behandlung seiner Nukleinsäure in vitro. Z. indukt. Abstamm.- u. Vererb.-Lehre88, 115 (1958).

    Google Scholar 

  • Nakada, D., E. Strelzoff, R. Rudner andF. J. Ryan: Is DNA replication a necessary condition for mutation?. Z. Vererb.-Lehre91, 210–213 (1960).

    Google Scholar 

  • Okada, T., K. Yanagisawa andF.J. Ryan: Elective production of thymineless mutants. Nature (Lond.)188, 340–341 (1960).

    Google Scholar 

  • Pontecorvo, G.: Trends in genetic analysis. New York: Columbia University Press 1958.

    Google Scholar 

  • Price, T. D.: Personal communication 1960.

  • Reiner, B., andS. Zamenhof: Studies on the chemically reactive groups of deoxyribonucleic acids. J. biol. Chem.228, 475–486 (1957).

    Google Scholar 

  • Rose, I. A., andB. S. Schweigert: Incorporation of C14 totally labeled nucleosides into nucleic acids. J. biol. Chem.202, 635–645 (1953).

    Google Scholar 

  • Rudner, R.: Mutation as an error in base paring. II. Kinetics of 5-bromodeoxyuridine and 2-aminopurine-induced mutagenesis. Z. Vererb.-Lehre 1961, in press.

  • —, andE. Balbinder: Reversion induced by base analogues inSalmonella typhimurium. Nature (Lond.)186, 180 (1960).

    Google Scholar 

  • Schuster, H., andG. Schramm: Bestimmung der biologisch wirksamen Einheit in der Ribonukleinsäure des TMV auf chemischem Wege. Z. Naturforsch.13b, 697 (1958).

    Google Scholar 

  • Shapiro, H. S., andE. Chargaff: Severe distortion by 5-bromouracil of the sequence characteristics of a bacterial deoxyribonucleic acid. Nature (Lond.)188, 62–63 (1960).

    Google Scholar 

  • Smith, J. D., andG. R. Wyatt: The composition of some microbial deoxypentose nucleic acid. Biochem. J.49, 144–148 (1951).

    Google Scholar 

  • Strauss, B., andS. Okubo: Protein synthesis and the induction of mutation inEscherichia coli by alkylating agents. J. Bact.79, 464–473 (1960).

    Google Scholar 

  • Strelzoff, E.: Personal communication 1960.

  • Tessman, I.: Mutagenesis in phage ΦX174 and T4 and properties of the genetic material. Virology9, 375–385 (1959).

    Google Scholar 

  • Tsubbi, K. K., andT. D. Price: Isolation, detection and measure of microgram quantities of labeled tissue nucleotide. Arch. Biochem.81, 223–237 (1959).

    Google Scholar 

  • Vielmetter, V. W., andH. Schuster: The base specificity of mutation induced by nitrous acid in phage T2. Biochem. Biophys. Res. Commun.2, 234–328 (1960).

    Google Scholar 

  • Visher, E., andE. Chargaff: The separation and quantitative estimation of purines and pyrimidines in minute amounts. J. biol. Chem.176, 703–714 (1948).

    Google Scholar 

  • Wacker, A., S. Kirschfeld andT. Lothur: Über den Einbau purineanalgger Verbindungen in die Bakteriennukleinsäure. J. Mol. Biol.2, 241–242 (1960).

    Google Scholar 

  • —,A. Trebst, D. Jacherts andF. Weygand: Über den Einbau von 5-Bromouracil-[2-14C] in die Desoxyribonucleinsäure verschiedener Bakterien. Z. Naturforsch.6b, 161–617 (1954).

    Google Scholar 

  • Watson, J. D., andF. H. C. Crick: Genetical implications of the structure of deoxyribonucleic acid. Nature (Lond.)171, 964–969 (1953).

    Google Scholar 

  • Way, J. L., andR. E. J. Parks: Enzymatic synthesis of 5-phosphate nucleotides of purines analogues. J. biol. Chem.231, 467–480 (1958).

    Google Scholar 

  • Witkin, E. M.: Time, temperature and protein synthesis. A study of ultraviolet-induced mutation in bacteria. Cold Spr. Harb. Symp. quant. Biol.21, 123–140 (1956).

    Google Scholar 

  • Yanofsky, C.: The tryptophan synthetase system. Bact. Rev.24, 221–245 (1960).

    Google Scholar 

  • Zamenhof, S., R. Degiovanni andK. Rich:Escherichia coli containing unnatural pyrimidines in its deoxyribonucleic acid. J. Bact.71, 60–69 (1956).

    Google Scholar 

  • —, andS. Greer: Heat as an agent producing high frequency of mutations and unstable genes inEscherichia coli. Nature (Lond.)182, 611–613 (1958).

    Google Scholar 

  • —, andG. Griboff:E. coli containing 5-bromouracil in its deoxyribonucleic acid. Nature (Lond.)174, 307–308 (1954).

    Google Scholar 

  • Zamenhof, S.,B. Reiner, R. Degiovanni andK. Rich: Introduction of unnatural pyrimidines into deoxyribonucleic acid ofEscherichia coli. J. biol. Chem.219, 165–173.

  • —,K. Rich andR. Degiovanni: Further studies on the intro- of pyrimidines into deoxyribonucleic acid ofEscherichia coli. J. biol. Chem.232, 651–657 (1958).

    Google Scholar 

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I dedicate this and the following paper to my teacher, Prof.L. C. Dunn.

With 7 Figures in the Text

Supported in part by grants from the “American Cancer Society, the U.S. Public Health Service” and the “National Science Foundation” administered by ProfessorF. J. Ryan.

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Rudner, R. Mutation as an error in base pairing. Zeitschrift für Vererbungslehre 92, 336–360 (1961). https://doi.org/10.1007/BF00890057

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