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Methylation-Instructed Mismatch Correction as a Postreplication Error Avoidance Mechanism in Escherichia Coli

  • Chapter
Molecular and Cellular Mechanisms of Mutagenesis

Summary

The error rate for DNA replication in Escherichia coli has been estimated as one error per 108−1011 base pairs replicated. This level of accuracy is considerably higher than that predicted on the basis of free-energy calculations or that achieved by DNA polymerases in vitro. The existence of an excision repair mechanism acting upon mismatched base pairs could account, at least in part, for the accuracy achieved in vivo. Such a repair mechanism has been postulated to account for a number of genetic observations related to gene conversion and high negative interference phenomena. Furthermore, the increased spontaneous mutability of Pnemococcus hex - and E. coli uvrE - mutants that appear to be deficient in the repair of some mismatched base pairs indicates the involvement of mismatch repair in the suppression of spontaneous mutation rates, The existence of a mismatch repair system capable of efficiently correcting mispaired bases implies that a strand discrimination system must exist which allows the discrimination between the “incorrect” newly synthesized daughter strand and the “correct original parental strand.

As DNA methylation is a postreplicational process (i.e., newly synthesized strands are undermethylated). DNA methylation is one possible mechanism allowing the discrimination between parental and daughter DNA strands. In accordance with this hypothesis is the observation that dam mutants that are deficient in 6-methyladenine residues occurring at the 5′G-A-T-C3′ sequence are spontaneous mutators. These strains are also hypermutable by base analogs, e.g. 2-aminopurine.

Further mutants of E. coli have been isolated that are defective in mismatch repair. These mutants, which include mutH, mutL, mutS and uvrE, increase spontaneous base transition and frameshift rates by as much as 103. These mutations also affect the level of negative interference seen in phage crosses for closely linked markers as well as cellular sensitivity to alkylating agents. More direct evidence in favor of the above hypothesis has been obtained from phage a heteroduplex assays where the DNA strands are specifically methylated or nonmethylated. These experiments show the preferential loss of the genetic marker carried on the nonmethylated DNA strand consistent with this hypothesis.

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References

  • Ahmad, A., Holloman, W. K., and Holliday, R., 1975, Nuclease that preferentially inactivates DNA containing mismatched bases, Nature, 258: 54.

    Article  PubMed  CAS  Google Scholar 

  • Argwal, S. S., Duke, D. K., and Loeb, L. A., 1979, On the fidelity of DNA replication: Accuracy of Escherichia coli DNA polymerase I, J. Biol. Chem., 254: 101.

    Google Scholar 

  • Baker, M. S., and Topal, M. D., 1981, Cellular DNA precursor triphosphates are targets of MNU, J. Supramol. Struc. Suppl., 5 (Cell Biochem.), 170.

    Google Scholar 

  • Bale, A., d’Alarcao, M., and Marinus, M. G., 1979, Characterization of DNA adenine methylation mutants of Escherichia coli K12, Mutat. Res., 59: 157.

    Article  PubMed  CAS  Google Scholar 

  • Baas, P. D., and Jansz, H. S., 1972, Asymmetric information transfer during ϕX174 DNA replication, J. Mol. Biol., 63: 557.

    Article  PubMed  CAS  Google Scholar 

  • Boehm, T. L., and Drahovsky, D., 1979, Effect of carcinogen ethionine on enzymatic methylation of DNA sequences with various degrees of repetitiveness, Eur. J. Cancer, 15: 1167.

    Article  PubMed  CAS  Google Scholar 

  • Bridges, B. A., and Mottershead, R. P., 1978, Mutagenic DNA repair in Escherichia coli. VII. Constitutive and inducible manifestations, Mutat. Res., 52: 151.

    Article  PubMed  CAS  Google Scholar 

  • Clayton, L. K., Goodman, M. F., Branscomb, E. W., and Galas, D. J., 1979, Error induction and correction by mutant and wild type T4 DNA polymerases, J. Biol. Chem., 254: 1902.

    PubMed  CAS  Google Scholar 

  • Coulondre, C., and Miller, J. H., 1977a, Genetic studies of the lac repressor. III. Additional correlation of mutational sites with specific amino acid residues, J. Mol. Biol., 117: 525.

    Article  PubMed  CAS  Google Scholar 

  • 10.Coulondre, C., and Miller, J. H., 1977b, Genetic studies of the lacI repressor, IV. Mutagenic specificity of the lacl gene of Escherichia coli, J. Mol. Biol., 117: 577.

    Article  Google Scholar 

  • Cox, E. C., 1976, Bacterial mutator genes and the control of spontaneous mutation, Annu. Rev. Genet., 10: 135.

    Article  PubMed  CAS  Google Scholar 

  • Cox, R., and Irving, Ch. C., 1977, Inhibition of DNA methylation by S-adenosylethionine with the production of methyl-deficient DNA in regenerating rat liver, Cancer Res., 37: 222.

    PubMed  CAS  Google Scholar 

  • Dohet, C., Bourguignon-Van Hören, M. F., and Radman, M., 1981, Mismatch correction mutants: Their effect on lambda recombination, Proc. Natl. Acad. Sci. U.S.A., submitted

    Google Scholar 

  • Drake, J. W., 1969, “The Molecular Basis of Mutation,” Holden-Day, San Francisco.

    Google Scholar 

  • Drake, J. W., 1981, Perspectives in molecular mutagenesis, this volume.

    Google Scholar 

  • Eckardt, F., and Haynes, R. H., 1977, Induction of pure and sectored mutant clones in excision-proficient and deficient strains of yeast, Mutat. Res., 43: 327.

    Article  PubMed  CAS  Google Scholar 

  • Fiftcham, J. R. S., and Holliday, R., 1970, An explanation of fine structure map expansion in terms of excision repair, Mol. Gen. Genet., 109: 307.

    Google Scholar 

  • Glickman, B. W., 1979, Spontaneous mutagenesis in Escherichia coli strains lacking 6-methyladenine residues in their DNA: An altered mutational spectrum in dam- mutants, Mutat. Res., 61: 153.

    Article  PubMed  CAS  Google Scholar 

  • Glickman, B. W., and Radman, M., 1980, Escherichia coli mutator mutants deficient in methylation-instructed DNA mismatch correction, Proc. Natl. Acad. Sci. U.S.A., 77: 1063.

    Article  PubMed  CAS  Google Scholar 

  • Glickman, B. W., Van der Elsen, P., and Radman, M., 1978, Induced mutagenesis in dam- mutants of Escherichia coli: A role for 6- methyladenine in mutation avoidance, Mol. Gen. Genet., 163: 307.

    Article  PubMed  CAS  Google Scholar 

  • Gomez-Eichelmann, M. C., 1979, DNA adenine and cytosine methylation in Salmonella typhimurium and Salmonella typhi, J. Bacteriol., 140: 574.

    PubMed  CAS  Google Scholar 

  • Haefner, K., 1968, Concerning the mechanism of ultraviolet mutagenesis. A micromanipulatory pedigree analysis in Schizo- saccharomyces pombe, Genetics, 57: 169.

    Google Scholar 

  • Hanawalt, P. C., Cooper, P. K., Ganesan, A. K., and Smith, C. A., 1979, DNA repair in bacteria and mammalian cells, Annu. Rev. Biochem., 48: 783.

    Article  PubMed  CAS  Google Scholar 

  • Hannan, M. A., Duck, P., and Nasim, A., 1976, UV-induced lethal sectoring and pure mutant clones in yeast, Mutat, Res., 36: 171.

    Article  CAS  Google Scholar 

  • Herman, G. E., and Modrich, P., 1981, Escherichia coli K-12 colonies that overproduce dam methylase are hypermutable, J. Bacteriol., 145: 644.

    PubMed  CAS  Google Scholar 

  • Hibner, U., and Alberts, B. M., 1980, Fidelity of DNA replication catalyzed in vitro on a natural DNA template by the T4 bacteriophage multienzyme complex, Nature, 285: 300.

    Article  PubMed  CAS  Google Scholar 

  • Holliday, R. A., 1964, A mechanism for gene conversion in fungi, Genet. Res., 5: 282.

    Article  Google Scholar 

  • James, A. P., and Kilbey, B. J., 1977, The timing of UV mutagenesis in yeast: A pedigree analysis of induced recessive mutation, Genetics, 87:237,

    PubMed  CAS  Google Scholar 

  • Kato, T., and Shinoura, Y., 1977, Isolation and characterization of mutants of Escherichia coli deficient in induction of mutations by ultraviolet light, Mol. Gen. Genet., 156: 121.

    PubMed  CAS  Google Scholar 

  • Knaap, Ada G. A. C., Glickman, B. W., and Simons, J. W. I. M., 1981, Effects of ethionine on the replicational fidelity in V-79 Chinese hamster cells, Mutat. Res., in press.

    Google Scholar 

  • Kubitschek, H., 1964, Mutation without segregation, Proc. Natl. Acad. Sci. U.S.A., 52: 1374.

    Article  PubMed  CAS  Google Scholar 

  • Lacks, S., and Greenberg, B., 1977, Complementary specificity of restriction endonucleases of Diplococcus pneumoniae with respect to methylation, J. Mol. Biol., 114: 153.

    Article  PubMed  CAS  Google Scholar 

  • Loeb, L. A., 1974, DNA replication fidelity, in: “The Enzymes,” H. D. Boyer, ed., Academic Press, New York.

    Google Scholar 

  • Marinus, M. G., 1976, Adenine methylation of Okazaki fragments in Escherichia coli map, J. Bacteriol., 128: 853.

    PubMed  CAS  Google Scholar 

  • Marinus, M. G., and Konrad, B., 1976, Hyper-recombination in dam mutants of Escherichia coli K-12, Mol. Gen. Genet., 149: 273.

    Article  PubMed  CAS  Google Scholar 

  • Marinus, M. G., and Morris, R. N., 1975, Pleiotropic effects of a DNA adenine methylation mutation (dam-3) in Escherichia coli K12, Mutat. Res., 28: 15.

    Article  PubMed  CAS  Google Scholar 

  • McGraw, B. R., and Marinus, M. G., 1980, Isolation and characterization of Dam+ revertants and suppressor mutations that modify secondary phenotypes of dam-3 strains of E. coli K-12, Mol. Gen. Genet., 178:309.

    Article  PubMed  CAS  Google Scholar 

  • Mohn, G. R., Guijt, N., and Glickman, B. W., 1980, Influence of DNA adenine methylation dam mutation and of plasmid PKM101 on the spontaneous and induced mutability of certain genes in Escherichia coli K-12, Mutat. Res., 74: 255.

    CAS  Google Scholar 

  • Mortelmans, K. E., and Stocker, B. A. D., 1976, Ultraviolet light protection, enhancement of ultraviolet mutagenesis and mutator effect of plasmid R46 in Salmonella typhimurium, J. Bacteriol., 128: 271.

    PubMed  CAS  Google Scholar 

  • Nasim, A., and Auerbach, C., 1967, The origin of complete and mosaic mutants from mutagenic treatment of single cells, Mutat. Res., 4: 1.

    Article  PubMed  CAS  Google Scholar 

  • Nevers, P., and Spatz, H., 1975, Escherichia coli mutants uvrD and uvrE deficient in gene conversion of λ-heteroduplexes, Mol. Gen. Genet., 139: 233.

    PubMed  CAS  Google Scholar 

  • Pukkila, P. J., 1978, The recognition of mismatched base pairs in DNA by DNase I from Ustilago maydis, Mol. Gen. Genet., 161: 245.

    Article  PubMed  CAS  Google Scholar 

  • Pukkila, P. J., Peterson, J., Herman, G., Modrich, P., and Meselson, M., 1981, Changes in the amount of DNA methylation influence mismatch correction, Proc. Natl. Acad. Sci. U.S.A., in press.

    Google Scholar 

  • Radman, M., 1975, SOS repair hypothesis: Phenomenology of inducible repair which is accompanied by mutagenesis, in: “Molecular Mechanisms for the Repair of DNA,” P. C. Hanawalt, and R. B. Setlow, eds., Plenum Press, New York,

    Google Scholar 

  • Radman, M., Villani, G., Boiteux, S., Defais, M., Caillet-Fauquet, P., and Spidari, S., 1977, On the molecular mechanism of induced mutagenesis, in: “Origins of Human Cancer,” H. Hiatt, J. D. Watson, and J. D. Winstein, eds., Cold Spring Harbor Laboratory, New York.

    Google Scholar 

  • Radman, M., Wagner, R. E., Glickman, B. W., and Meselson, M., 1980, DNA methylation, mismatch correction and genetic stability, in: “Progress in Environmental Mutagenesis,” M. Alacevic, ed., Elsevier-North Holland, Amsterdam.

    Google Scholar 

  • Razin, A., and Riggs, A. D., 1980, DNA methylation and gene function, Science, 210: 604.

    Article  PubMed  CAS  Google Scholar 

  • Ripley, L. S., 1981, Mutagenic specificity of nitrosomethylurea in bacteriophage T4, Mutat. Res., in press.

    Google Scholar 

  • Rydberg, B., 1977, Bromouracil mutagenesis in Escherichia coli: Evidence for involvement of mismatch repair, Mol. Gen. Genet., 152: 19.

    Article  PubMed  CAS  Google Scholar 

  • Rydberg, B., 1978, Bromouracil mutagenesis and mismatch repair in mutator strains of Escherichia coli, Mutat. Res., 52: 11.

    Article  PubMed  CAS  Google Scholar 

  • Samson, L., and Cairns, J., 1979, A new pathway for DNA repair in Escherichia coli, Nature, 267: 281.

    Google Scholar 

  • Taylor, J. H., 1979, “Molecular Genetics, Part 3, Chromosome Structure,” Academic Press, New York.

    Google Scholar 

  • Tiraby, J. G., and Fox, M. S., 1973, Marker discrimination in transformation and mutation of pneumococcus, Proc. Natl. Acad. Sci. U.S.A., 70: 3541.

    Article  PubMed  CAS  Google Scholar 

  • Todd, P. A., Brouwer, J., and Glickman, B. W., 1981, Influence of DNA repair deficiences on MMS and EMS induced mutagenesis in IS. coli K-12, Mutat. Res., in press.

    Google Scholar 

  • Topal, M. D., and Fresco, J. R., 1976, Complementary base pairing and the origin of substitution mutations, Nature (London), 263: 285.

    Article  CAS  Google Scholar 

  • Wagner, Jr., R., and Meselson, M., 1976, Repair tracts in mismatches DNA heteroduplexes, Proc. Natl. Acad. Sci. U.S.A., 73: 4135.

    Article  PubMed  CAS  Google Scholar 

  • Walker, G. C., 1977, Plasmid (pKMlOl)-mediated enhancement of repair and mutagenesis. Dependence on chromosomal genes in Escherichia coli K-12, Mol. Gen. Genet., 152: 93.

    Article  PubMed  CAS  Google Scholar 

  • Watson, J. D., and Crick, F. H. C., 1953, A structure for deoxyribose nucleic acids, Nature (London), 171: 737.

    Article  CAS  Google Scholar 

  • White, R., and Fox, M., 1974, Genetic consequences of transfection with heteroduplex bacteriophage λ DNA, Mol. Gen. Genet., 141: 163.

    Article  Google Scholar 

  • Whitehouse, H. L. K., and Hastings, P. J., 1965, The analysis of genetic recombination on the poloron hybrid DNA model, Genet. Res., 6: 27.

    Article  Google Scholar 

  • Wildenberg, J., and Meselson, M., 1975, Mismatch repair in hetero-duplex DNA, Proc. Natl. Acad. Sci. U.S.A., 72: 2202.

    Article  PubMed  CAS  Google Scholar 

  • Wilson, J. H., 1977, Genetic analysis of host range mutant viruses suggests an uncoating defect in simian virus 40-resistant monkey cells, Proc. Natl Acad. Sci. U.S.A., 74: 3503.

    Article  PubMed  CAS  Google Scholar 

  • Witkin, E. M., 1976, Ultraviolet mutagenesis and inducible DNA repair in Escherichia coli, Bacteriol. Rev., 40: 869.

    PubMed  CAS  Google Scholar 

  • Witkin, E. M., and Sicurella, N. A., 1974, Pure clones of lactose- negative mutants obtained in Escherichia coli after treatment with 5-bromouracil, J. Mol. Biol., 8: 610.

    Article  Google Scholar 

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Authors and Affiliations

  1. National Institute for Environmental Health Sciences, P. O. Box 12233, Research Triangle Park, North Carolina, 27709, USA

    B. W. Glickman

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  1. Oak Ridge National Laboratory, Oak Ridge, Tennessee, USA

    J. F. Lemontt  & W. M. Generoso  & 

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Glickman, B.W. (1982). Methylation-Instructed Mismatch Correction as a Postreplication Error Avoidance Mechanism in Escherichia Coli . In: Lemontt, J.F., Generoso, W.M. (eds) Molecular and Cellular Mechanisms of Mutagenesis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-3476-7_3

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  • DOI: https://doi.org/10.1007/978-1-4613-3476-7_3

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