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Effect of Variations in the Conditions of DNA Synthesis upon the Accuracy of DNA Replication

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Genetic Consequences of Nucleotide Pool Imbalance

Part of the book series: Basic Life Sciences ((BLSC,volume 31))

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Abstract

Recent refinements in the methods for measurement of accuracy of DNA replication have led to accurate estimates for a number of mispairs during the duplication of natural DNA for bacterial and mammalian DNA polymerases and for E. coli and bacteriophage T4 multienzyme replication complexes (see Refs. 17 and 25 for recent reviews). Using a combination of seven purified replication proteins of phage T4 (the products of genes 32, 41, 43, 44, 45, 61, and 62) to replicate DNA in vitro, it has been shown that the accuracy of this complex is very similar to that seen during replication of ΦX174 DNA in vivo [12, 16, 23–25]. DNA sequences (such as am33) that are replicated with a low accuracy in vivo show high error rates during replication in vitro. Other sequences (such as am16 and am9), which have a low reversion rate in vivo, are replicated with comparably high accuracy in vitro [23–25]. It has also been shown that by the appropriate use of deoxynucleotide pool biases, it is possible to induce reversions of a given amber mutant by specific transition and transversion pathways [12, 23, 24]. We have examined the influence of a variety of perturbations in the conditions of DNA replication in vitro, on the rates of formation of mispairs leading to transition and transversion mutations. These results are summarized here.

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References

  1. S. Benzer and E. Freese, Induction of specific mutations with 5-bromouracil, Proc. Natl. Acad. Sci., U.S.A., 44: 112 – 119 (1958).

    Article  PubMed  CAS  Google Scholar 

  2. M. Bittner, R. L. Burke, and B. Alberts, Purification of the T4 gene 32 protein free from detectable deoxyribonuclease activities, J. Biol. Chem., 254: 9565 – 9572 (1979).

    PubMed  CAS  Google Scholar 

  3. L. K. Clayton, M. F. Goodman, E. W. Branscomb, and D. J. Galas, Error induction and correction by mutant and wild type T4 DNA polymerases. Kinetic error discrimination mechanisms, J. Biol. Chem., 253: 1902 – 1912 (1979).

    Google Scholar 

  4. M. Demerec and J. Hanson, Mutagenic action of manganous chloride, Cold Spring Harbor Symp. Quant. Biol., 16: 215 – 227 (1951).

    Article  CAS  Google Scholar 

  5. A. R. Fersht, Fidelity of replication of phage ΦX174 by DNA polymerase III holoenzyme: spontaneous mutation by misincorporation, Proc. Natl. Acad. Sci., U.S.A., 76: 4946 – 4950 (1979).

    Article  PubMed  CAS  Google Scholar 

  6. A. R. Fersht and J. W. Knill-Jones, DNA polymerase accuracy and spontaneous mutation rates: frequencies of purine:purine, purine-pyrimidine, and pyrimidine-pyrimidine mismatches during DNA replication, Proc. Natl. Acad. Sci., U.S.A., 78: 4251 – 4255 (1981).

    Article  PubMed  CAS  Google Scholar 

  7. A. R. Fersht, J. W. Knill-Jones, and W. C. Tsui, Kinetic basis for spontaneous mutation. Misinsertion frequencies, proofreading specificities and cost of proofreading by DNA polymerases of E. coli, J. Mol. Biol., 156: 37 – 52 (1982).

    Article  PubMed  CAS  Google Scholar 

  8. A. R. Fersht and J. W. Knill-Jones, Fidelity of replication of bacteriophage ΦX174 DNA in vitroand in vivo, J. Mol. Biol., 165: 633 - 654 (1983).

    Article  PubMed  CAS  Google Scholar 

  9. E. Freese, The difference between spontaneous and base analog induced mutations in phage T4, Proc. Natl.. Acad. Sci., U.S.A., 45: 622 – 633 (1959).

    Article  PubMed  CAS  Google Scholar 

  10. E. Freese, The specific mutagenic effect of base analogs on phage T4, J. Mol. Biol., 1: 87 – 105 (1959).

    Article  CAS  Google Scholar 

  11. Z. W. Hall and I. R. Lehman, An in vitrotransversion by a mutationally altered T4-induced DNA polymerase, J. Mol. Biol., 36: 321 – 333 (1968).

    Article  PubMed  CAS  Google Scholar 

  12. U. Hibner and B. Alberts, Fidelity of DNA replication catalyzed in vitroon natural DNA template by the T4 bacteriophage multienzyme complex, Nature, 285: 300 – 305 (1980).

    Article  PubMed  CAS  Google Scholar 

  13. A. Kornberg, DNA Replication, W. H. Freeman, San Francisco (1980).

    Google Scholar 

  14. T. Kunkel and L. A. Loeb, On the fidelity of DNA replication. Effect of divalent metal ion activators and deoxynucleoside triphosphate pools on in vitromutagenesis, J. Biol. Chem., 255: 9961 – 9966 (1979).

    Google Scholar 

  15. T. A. Kunkel, R. M. Schaaper, R. Beckman, and L. A. Loeb, On the fidelity of DNA replication. Effect of the next nucleotide on proofreading, J. Biol. Chem., 256: 9883 – 9889 (1981).

    PubMed  CAS  Google Scholar 

  16. C. C. Liu, R. L. Burke, J. Barry, U. Hibner, and B. Alberts, Probing DNA replication mechanisms with the T4 bacteriophage in vitro, Cold Spring Harbor Symp. Quant. Biol., 43: 469 – 487 (1979).

    Article  PubMed  CAS  Google Scholar 

  17. L. A. Loeb and T. A. Kunkel, Fidelity of DNA synthesis, Ann. Rev. Biochem., 52: 429 – 457 (1982).

    Article  Google Scholar 

  18. C. F. Morris, L. A. Moran, and B. M. Alberts, Purification of gene 41 protein of bacteriophage T4, J. Biol. Chem., 254: 6797 – 6802 (1979).

    PubMed  CAS  Google Scholar 

  19. C. F. Morris, D. C. Mace, H. Hama-Inaba, N. Sinha, and B. Alberts, Purification of the gene 43, 44, 45, and 62 proteins of the bacteriophage T4 DNA replication apparatus, J. Biol. Chem., 254: 6787 – 6796 (1979).

    PubMed  CAS  Google Scholar 

  20. A. Orgel and L. E. Orgel, Induction of mutations in bacteriophage T4 with divalent manganese, J. Mol. Biol., 14: 453 – 457 (1965).

    Article  PubMed  CAS  Google Scholar 

  21. C. W. Shearman and L. A. Loeb, On the fidelity of DNA replication. Mechanisms of misincorporation by intercalating agents, J. Biol. Chem., 258: 4485 – 4491 (1983).

    PubMed  CAS  Google Scholar 

  22. N. K. Sinha, C. F. Morris, and B. M. Alberts, Efficient in vitroreplication of double-stranded DNA templates by a purified T4 bacteriophage system, J. Biol. Chem., 255: 4290 – 4303 (1980).

    PubMed  CAS  Google Scholar 

  23. N. K. Sinha and M. Haimes, Probing the mechanism of transition and transversion mutagenesis using the phage T4 DNA replication apparatus, in: “Mechanistic Studies of DNA Replication and Genetic Recombination” (B. Alberts, ed.), ICN-UCLA Symp. Molec. Cell Biol., 19:707–723 (1980)

    Google Scholar 

  24. N. K. Sinha and M. Haimes, Molecular mechanism of substitution mutagenesis. An experimental test of the Watson-Crick and Topal-Fresco models of base mispairings, J. Biol. Chem., 256: 10671 – 10683 (1981).

    PubMed  CAS  Google Scholar 

  25. N. K. Sinha and M. F. Goodman, Fidelity of DNA replication, in: “The Bacteriophage T4” (C. Mathews, E. Kutter, G. Mosig, and P. Berget, eds.), ASM Press, Washington, D.C., 131–137 (1983)

    Google Scholar 

  26. M. A. Sirover and L. A. Loeb, Infidelity of DNA synthesis in vitro: screening for potential metal mutagens or carcinogens, Science, 194: 1434 – 1436 (1976).

    Article  PubMed  CAS  Google Scholar 

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© 1985 Plenum Press, New York

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Razzaki, T., Sinha, N.K. (1985). Effect of Variations in the Conditions of DNA Synthesis upon the Accuracy of DNA Replication. In: de Serres, F.J. (eds) Genetic Consequences of Nucleotide Pool Imbalance. Basic Life Sciences, vol 31. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2449-2_11

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  • DOI: https://doi.org/10.1007/978-1-4613-2449-2_11

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-9488-7

  • Online ISBN: 978-1-4613-2449-2

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