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Recombinational repair of alkylation lesions in phage T4

I. N-methyl-N′-nitro-N-nitrosoguanidine

Summary

Treatment of phage T4-host adsorption complexes by MNNG1 increased recombination between two rII markers by about three-fold. Temperature sensitive mutants defective in genes 32, 46 and 47, which cause reductions in recombination at semirestrictive temperatures, proved to be substantially more sensitive to MNNG at such temperatures than wild-type phage. In addition, the recombination defective mutants x m(uvsX) and y 10(y) were more sensitive to MNNG than wild-type, whereas mutants defective in genes 45 and denV, which are apparently not involved in recombination, were not MNNG sensitive. These findings suggest that a recombination pathway involving the products of genes 32, 46, 47, uvsX and y is employed in repairing MNNG-induced lethal lesions. This mechanism is effective in cells infected by single phage, implying post-replication recombinational repair between daughter chromosomes. MNNG-induced lesions are subject to multiplicity reactivation, but mutants defective in genes 46 or 47 showed the same degree of multiplicity reactivation as wild-type phage. The gene 32 and gene 47 recombination defective mutants were tested for their effects on MNNG-induced reversion of an rII marker. No reduction in induced reversion was found. Thus, it appears that the postulated recombinational repair pathway employing the products of genes 32 and 47 does not contribute substantially to induced mutagenesis.

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References

  1. Abbadessa, R., Burdick, A.B.: The effect of x-irradiation on somatic crossing over in Drosophila melanogaster. Genetics 48, 1345–1356 (1963)

  2. Adams, M.H.: Bacteriophages. New York: Interscience Publishers, Inc. 1959

  3. Alberts, B.M., Amodio, F.J., Jenkins, M., Guttmann, E.D., Ferris, F.L.: Studies with DNA-cellulose chromatography. I. DNA-binding proteins from Escherichia coli. Cold Spr. Harb. Symp. quant. Biol. 33, 289–305 (1968)

  4. Baker, R., Tessman, I.: Different mutagenic specificities in phages S13 and T4: in vivo treatment with N-methyl-N′-nitro-N-nitrosoguanidine. J. molec. Biol. 35, 439–448 (1968)

  5. Berger, H., Warren, A.J., Fry, K.E.: Variations in genetic recombination due to amber mutations in T4D bacteriophage. J. Virol. 3, 171–175 (1969)

  6. Bernstein, C., Bernstein, H., Mufti, S., Strom, B.: Stimulation of mutation in phage T4 by lesions in gene 32 and by thymidine imbalance. Mutation Res. 16, 113–119 (1972)

  7. Bernstein, C., Morgan, D., Gensler, H.L., Schneider, S., Holmes, G.E.: The dependence of HNO2 mutagenesis in phage T4 on ligase and the lack of dependence of 2AP mutagenesis on repair functions. Molec. gen. Genet. 148, 213–220 (1976)

  8. Bernstein, H.: Repair and recombination in phage T4. I. Genes affecting recombination. Cold Spr. Harb. Symp. quant. Biol. 33, 325–338 (1968)

  9. Bernstein, H.: Germ line recombination may be primarily a manifestation of DNA repair processes. J. theoret. Biol. 69, 371–380 (1977)

  10. Boyle, J.M., Symonds, N.: Radiation-sensitive mutants of T4D. I. T4y: A new radiation:sensitive mutant; effect of the mutant on radiation survival, growth and recombination. Mutation Res. 8, 431–439 (1969)

  11. Champe, S.P., Benzer, S.: Reversal of mutant phenotypes by 5-fluorouracil: an approach to nucleotide sequences in messenger-RNA. Proc. nat. Acad. Sci. (Wash.) 48, 532–545 (1962)

  12. 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)

  13. Davis, K.J., Symonds, N.: The pathway of recombination in phage T4. Molec. gen. Genet. 132, 173–180 (1974)

  14. Dugle, D.L., Campbell, C.E., Meeker, B.E., Gillespie, C.J.: Correlation between lethality and DNA single-strand breaks in Bacillus subtilis cells treated with N-methyl-N′-nitro-N-nitrosoguanidine. Mutation Res. 18, 237–245 (1973)

  15. Dulbecco, R.: A critical test of the recombination theory of multiplicity reactivation. J. Bact. 63, 119–207 (1952)

  16. Epstein, R.H.: A study of multiplicity-reactivation in bacteriophage T4 I. Genetic and functional analysis of T4D-K12(λ) complexes. Virology 6, 382–404 (1958)

  17. Fisher, K.M., Bernstein, H.: Deficiency of double mutant recombinants in crosses of phage T4. Molec. gen. Genet. 106, 139–150 (1970)

  18. Friedberg, E.C.: Studies on the substrate specificity of the T4 excision repair endonuclease. Mutation Res. 15, 113–123 (1972)

  19. Friedberg, E.C., King, J.J.: Endonucleolytic cleavage of UV-irradiated DNA controlled by the v + gene of phage T4. Biochem. biophys. Res. Commun. 37, 646–651 (1969)

  20. Hamlett, N.V., Berger, H.: Mutations altering genetic recombination and repair of DNA in bacteriophage T4. Virology 63, 539–567 (1975)

  21. Harm, W.: Multiplicity reactivation, marker rescue, and genetic recombination in phage T4 following x-ray inactivation. Virology 5, 337–361 (1958)

  22. Harm, W.: Mutants of phage T4 with increased sensitivity to ultraviolet. Virology 19, 66–71 (1963)

  23. Harm, W.: On the control of UV-sensitivity of phage T4 by the gene x. Mutation Res. 1, 344–354 (1964)

  24. Hosoda, J.: Role of genes 46 and 47 in bacteriophage T4 reproduction III. Formation of joint molecules in biparental recombination. J. molec. Biol. 106, 277–284 (1976)

  25. Ishii, Y., Kondo, S.: Comparative analysis of deletion and base-change mutabilities of Escherichia coli B strains differing in DNA repair capacity (Wild-type, uvrA-, polA-, recA-) by various mutagens. Mutation Res. 27, 27–44 (1975)

  26. Jeggo, P., Defais, M., Samson, L., Schendel, P.: An adaptive response of E. coli to low levels of alkylating agent: Comparison with previously characterised DNA repair pathways. Molec. gen. Genet. 157, 1–9 (1977)

  27. Johns, V., Bernstein, C., Bernstein, H.: Recombinational repair of alkylation lesions in phage T4. II. Ethyl methanesulfonate. Molec. gen. Genet. 167, 197–207 (1978)

  28. Kirtikar, D.M., Catheart, G.R., Goldthwait, D.A.: Endonuclease II, apurinic acid endonuclease, and exonuclease III. Proc. nat. Acad. Sci. (Wash.) 73, 4324–4328 (1976)

  29. Kock, R.E., McGaw, M.K., Drake, J.W.: Mutator mutations in bacteriophage T4 gene 32 (DNA unwinding protein). J. Virol. 19, 490–494 (1976)

  30. Kondo, S., Ichikawa, H., Iwo, K., Kato, T.: Base-change mutagenesis and prophage induction in strains of Escherichia coli with different DNA repair capacities. Genetics 66, 187–217 (1970)

  31. LaPolla, J.P., Harris, C.M., Vary, J.C.: Properties of N-methyl-N′-nitro-N-nitrosoguanidine and its action on Bacillus subtilis transforming DNA. Biochem. biophys. Res. Commun. 49, 133–138 (1972)

  32. Lawley, P.D., Orr, D.J.: Specific excision of methylation products from DNA of Escherichia coli treated with N-methyl-N′-nitro-N-nitrosoguanidine. Chem. Biol. Interact. 2, 154–157 (1970)

  33. Lawley, P.D., Thatcher, C.J.: Methylation of deoxyribonucleic acid in cultured mammalian cells by N-methyl-N′-nitro-N-nitrosoguanidine. Biochem. J. 116, 693–707 (1970)

  34. Lindahl, T., Ljungquist, S.: Apurinic and apyrimidinic sites in DNA. In: Molecular mechanisms for repair of DNA (Hanawalt, P.C., Setlow, R.B., eds.). Part A, pp. 31–38. New York: Plenum Press 1975

  35. Ljungquist, S., Lindahl, T., Howard-Flanders, P.: Methyl methanesulfonate-sensitive mutant of Escherichia coli deficient in an endonuclease specific for apurinic sites in deoxyribonucleic acid. J. Bact. 126, 646–653 (1976)

  36. Loveless, A.: Genetic and allied effects of alkylating agents. University Park: The Penn. State Univ. Press 1966

  37. Loveless, A.: Possible relevance of 0–6 alkylation of deoxyguanosine to the mutagenicity and carcinogenicity of nitrosamines and nitrosamides. Nature (Lond.) 223, 206–207 (1969)

  38. Manny, T.R., Mortimer, R.K.: Allelic mapping in yeast by x-ray-induced mitotic reversion. Science 143, 581–583 (1964)

  39. Martensen, D.V., Green, M.M.: UV-induced mitotic recombination in somatic cells of Drosophila melanogaster. Mutation Res. 36, 391–396 (1976)

  40. Mattson, T.L.: Recombination of bacteriophage T4 stimulated by 9-aminocaridine. Genetics 65, 535–544 (1970)

  41. Minderhout, L. van, Grimbergen, J., Groot, B. de: Nonsense mutants in the baceriophage T4D v gene. Mutation Res. 29, 333–348 (1975)

  42. Nonn, E.M., Bernstein, C.: Multiplicity reactivation and repair of nitrous acid-induced lesions in baceriophage T4. J. molec. Biol. 116, 31–47 (1977)

  43. Prashad, N., Hosoda, J.: Role of genes 46 and 47 in bacteriophage T4 reproduction. II. Formation of gaps on parental DNA of polynucleotide ligase defective mutants. J. molec. Biol. 70, 617–635 (1972)

  44. Prudhommeau, C., Proust, J.: UV irradiation of polar cells of Drosophila melanogaster embryos. V. A study of the meiotic recombination in females with chromosomes of of different structure. Mutation Res. 23, 63–66 (1973)

  45. Rupp, W.D., Wilde, C.E. III, Reno, D.L., Howard-Flanders, P.: Exchanges between DNA strands in ultraviolet-irradiated Escherichia coli. J. molec. Biol. 61, 25–44 (1971)

  46. Ryttman, H., Zetterberg, G.: Induction of mitotic recombination with N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) in Saccharomyces cerevisiae. A comparison between treatment in vitro and in the host mediated assay. Mutation Res. 34, 201–216 (1976)

  47. Samson, L., Cairns, J.: A new pathway for DNA repair in Escherichia coli. Nature (Lond.) 267, 281–283 (1977)

  48. Steinberg, C.M., Edgar, R.S.: A critical test of a current theory of genetic recombination in bacteriophage. Genetics 47, 187–208 (1962)

  49. Strauss, B., Scudiero, D., Henderson, E.: The nature of the alkylation lesion in mammalian cells. In: Molecular mechanisms for repair of DNA (Hanawalt, P.C., Setlow, R.B., eds.), Part A, pp. 13–24. New York: Plenum Press 1975

  50. Streisinger, G.: The genetic control of ultraviolet sensitivity levels in bacteriophages T2 and T4. Virology 2, 1–12 (1956)

  51. Streisinger, G., Franklin, N.C.: Mutation and recombination at the host range genetic region of phage T2. Cold Spr. Harb. Symp. quant. Biol. 21, 103–111 (1956)

  52. Symonds, N., Ritchie, D.A.: Multiplicity reactivation after the decay of incorporated radioactive phosphorus in phage T4. J. molec. Biol. 3, 61–70 (1961)

  53. Tomizawa, J-I., Anraku, N., Iwama: Molecular mechanisms of genetic recombination in bacteriophage. VI. A mutant defective in the joining of DNA molecules. J. molec. Biol. 21, 247–253 (1966)

  54. Verly, W.G.: Monofunctional alkylating agents and apurinic sites in DNA. Biochem. Pharmacol. 23, 3–8 (1974)

  55. Warner, H.R., Hobbs, M.D.: Incorporation of uracil-14C into nucleic acids in Escherichia coli infected with bacteriophage T4 and T4 amber mutants. Virology 33, 376–384 (1967)

  56. Wilkie, D., Lewis, D.: The effect of ultraviolet light on recombination in yeast. Genetics 48, 1701–1716 (1963)

  57. Witkin, E.M.: Ultraviolet mutagenesis and inducible DNA repair in Escherichia coli. Bact. Rev. 40, 869–907 (1976)

  58. Wood, W.B., Revel, H.R.: The genome of bacteriophage T4. Bact. Rev. 40, 847–868 (1976)

  59. Wu, R., Geiduschek, E.P.: The role of replication proteins in the regulation of bacteriophage T4 transcription. I. Gene 45 and hydroxymethyl-C-containing DNA. J. molec. Biol. 96, 513–538 (1975)

  60. Yajko, D.M., Weiss, B.: Mutations simultaneously affecting endonuclease II and exonuclease III in Escherichia coli. Proc. nat. Acad. Sci. (Wash.) 72, 688–692 (1975)

  61. Yamamoto, K., Kondo, S., Sugimura, T.: Mechanism of potent mutagenic action of N-Methyl-N′-nitro-N-nitrosoguanidine on intracellular phage lambda. J. molec. Biol. 118, 413–430 (1978)

  62. Yasuda, S., Sekiguchi, M.: Mechanism of repair of DNA in bacteriophage. II. Inability of ultraviolet-sensitive strains of bacteriophage in inducing an enzyme activity to excise pyrimidine dimers. J. molec. Biol. 47, 243–255 (1970)

  63. Yost, H.T., Jr., Chaleff, R.S., Finerty, J.P.: Induction of mitotic recombination in Saccharomyces cerevisiae by ethyl methanesulfonate. Nature (Lond.) 215, 660–661 (1967)

  64. Zampieri, A., Greenberg, J., Warren, G.: Inactivating and mutagenic effects of 1-methyl-3-nitro-1-nitrosoguanidine on intracellular bacteriophage. J. Virol. 2, 901–904 (1968)

  65. Zimmermann, F.K., Schwaier, R.: Induction of mitotic gene conversion with nitrous acid, 1-methyl-3-nitro-1-nitrosoguanidine and other alkylating agents in Saccharomyces cerevisiae. Molec. gen. Genet. 100, 63–76 (1967)

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Communicated by A.J. Clark

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Schneider, S., Bernstein, C. & Bernstein, H. Recombinational repair of alkylation lesions in phage T4. Molec. Gen. Genet. 167, 185–195 (1978). https://doi.org/10.1007/BF00266912

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Keywords

  • Recombination
  • Alkylation
  • Repair Pathway
  • Adsorption Complex
  • Recombinational Repair