Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Timeline
  • Published:

The eureka enzyme: the discovery of DNA polymerase

Nature Reviews Molecular Cell Biology volume 7, pages 143–147 (2006)Cite this article

Abstract

The identification and partial purification by Arthur Kornberg and his colleagues in 1956 of an enzyme ? DNA polymerase I of Escherichia coli ? that catalysed the stable incorporation of deoxyribonucleotides into DNA in vitro came as a surprise. At the time, most scientists in the field believed that DNA synthesis was too complicated to be accurately reflected outside the living cell.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Arthur Kornberg, circa 1956 ? the year that he announced the discovery of DNA polymerase.
Figure 2: Arthur Kornberg with his sons Roger (left), Kenneth (next to his mother Sylvia) and Thomas (next to his father), circa 1959.

References

  1. Kornberg, A. For the Love of Enzymes: The Odyssey of a Biochemist. (Harvard University Press, Cambridge, Massachusetts, 1989).

    Google Scholar 

  2. Kornberg, A. Latent liver disease in persons recovered from catarrhal jaundice and in otherwise normal medical students, as revealed by the bilirubin excretion test. J. Clin. Invest. 21, 299?308 (1942).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kornberg, A. Never a dull enzyme. Annu. Rev. Biochem. 58, 1?30 (1989).

    Article  CAS  PubMed  Google Scholar 

  4. Watson, J. D. & Crick, F. C. A structure for deoxyribose nucleic acid. Nature 171, 737?738 (1953).

    Article  CAS  PubMed  Google Scholar 

  5. Kornberg, A. Biological synthesis of deoxyribonucleic acid. Science 131, 1503?1508 (1960).

    Article  CAS  PubMed  Google Scholar 

  6. Grunberg-Manago, M. & Ochoa, S. J. Enzymatic synthesis and breakdown of polynucleotides; polynucleotide phosphorylase. J. Am. Chem. Soc. 77, 3165?3166 (1955).

    Article  CAS  Google Scholar 

  7. Weiss, S. B. & Gladstone, L. A mammalian system for the incorporation of cytidine triphosphate into ribonucleic acid. J. Am. Chem. Soc. 81, 4118?4119 (1959).

    Article  CAS  Google Scholar 

  8. Lehman, I. R. Discovery of DNA polymerase. J. Biol. Chem. 278, 34743?34738 (2003).

    Article  Google Scholar 

  9. Kornberg, A., Lehman, I. R. & Simms, E. S. Polydesoxyribonucleotide synthesis by enzymes from Escherichia coli. Fed. Proc. 15, 291 (1956).

    Google Scholar 

  10. Kornberg, A. in The Chemical Basis of Heredity. (eds McElroy, W. D. & Glass, B.) 579?608 (Johns Hopkins Press, Baltimore, 1957).

    Google Scholar 

  11. Kornberg, A., Lehman, I. R., Bessman, M. J. & Simms, E. S. Enzymatic synthesis of desoxyribonucleic acid. Biochim. Biophys. Acta 21, 197?198 (1956).

    Article  CAS  PubMed  Google Scholar 

  12. Lehman, I. R., Bessman, M. J., Simms, E. S. & Kornberg, A. Enzymatic synthesis of deoxyribonucleic acid I. Preparation of substrates and partial purification of an enzyme from Escherichia coli. J. Biol. Chem. 233, 163?170 (1958).

    CAS  PubMed  Google Scholar 

  13. Bessman, M., Lehman, I. R., Simms, E. S. & Kornberg, A. Enzymatic synthesis of deoxyribonucleic acid II. General properties of the reaction. J. Biol. Chem. 233, 171?177 (1958).

    CAS  PubMed  Google Scholar 

  14. Adler, H. I., Fisher, W. D. & Stapleton, G. E. National Academy of Sciences. Abstracts of papers presented at the autumn meeting, Durham, North Carolina, 17?19 October 1966. Science 154, 417 (1966).

    Article  Google Scholar 

  15. Adler, H. I., Fisher, W. D., Cohen, A. & Harigree, A. A. Miniature Escherichia coli cells deficient in DNA. Proc. Natl Acad. Sci. USA 57, 321?326 (1967).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cohen, A., Fisher, W. D., Curtiss, R. 3rd & Adler, H. I. The properties of DNA transferred to minicells during conjugation. Cold Spring Harbor Symp. Quant. Biol. 33, 635?641 (1968).

    Article  CAS  PubMed  Google Scholar 

  17. Friedberg, E. C. Correcting the Blueprint of Life: An Historical Account of the Discovery of DNA Repair Mechanisms. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 1997).

    Google Scholar 

  18. De Lucia, P. & Cairns, J. Isolation of an E. coli strain with a mutation affecting DNA polymerase. Nature 224, 1164?1166 (1969).

    Article  CAS  PubMed  Google Scholar 

  19. Kornberg, T. & Gefter, M. L. DNA synthesis in cell-free extracts of a DNA polymerase-defective mutant. Biochem. Biophys. Res. Commun. 40, 1348?1355 (1970).

    Article  CAS  PubMed  Google Scholar 

  20. Knippers, R. DNA polymerase II. Nature 228, 1050?1053 (1970).

    Article  CAS  PubMed  Google Scholar 

  21. Moses, R. E. & Richardson, C. C. A new DNA polymerase activity of Escherichia coli. I. Purification and properties of the activity present in E. coli PolA1. Biochem. Biophys. Res. Commun. 40, 1557?1564 (1970).

    Article  Google Scholar 

  22. Kornberg, T. & Gefter, M. L. Purification and DNA synthesis in cell-free extracts: properties of DNA polymerase II. Proc. Natl Acad. Sci. USA 68, 761?764 (1971).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bollum, F. J. & Potter, V. R. Thymidine incorporation into deoxyribonucleic acid of rat liver homogenates. J. Am. Chem. Soc. 79, 3603?3604 (1957).

    Article  CAS  Google Scholar 

  24. Hubscher, U., Maga, G. & Spadari, S. Eukaryotic DNA polymerases. Annu. Rev. Biochem. 71, 133?163 (2002).

    Article  CAS  PubMed  Google Scholar 

  25. Kalf, G. F. & Ch'ih, J. J. Purification and properties of deoxyribonucleic acid polymerase from rat liver mitochondria. J. Biol. Chem. 243, 4904?4916 (1968).

    CAS  PubMed  Google Scholar 

  26. Meyer, R. R. & Simpson, M. V. DNA biosynthesis in mitochondria: partial purification of a distinct DNA polymerase from isolated rat liver mitochondria. Proc. Natl Acad. Sci. USA 61, 130?137 (1968).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Baltimore, D. RNA-dependent DNA polymerase in virions of RNA tumor viruses. Nature 226, 1209?1211 (1970).

    Article  CAS  PubMed  Google Scholar 

  28. Temin, H. M & Mizutani, S. RNA-dependent DNA polymerase in virions of Rous sarcoma virus. Nature 226, 1211?1213 (1970).

    Article  CAS  PubMed  Google Scholar 

  29. Echols, H. & Goodman, M. F. Fidelity mechanisms in DNA replication. Annu. Rev. Biochem. 60, 477?551 (1991).

    Article  CAS  PubMed  Google Scholar 

  30. Rajagopalan, M. et al. Activity of the purified mutagenesis proteins UmuC, UmuD', and RecA in replicative bypass of an abasic DNA lesion by DNA polymerase III. Proc. Natl Acad. Sci. USA 89, 10777?10781 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Tang, M. et al. UmuD'2C is an error-prone DNA polymerase, Escherichia coli pol V. Proc. Natl Acad. Sci. USA 96, 8919?8924 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Reuven, N. B., Arad, G., Maor-Shoshani, A. & Livneh, Z. The mutagenesis protein UmuC is a DNA polymerase activated by UmuD', RecA, and SSB and specialized for translesion synthesis. J. Biol. Chem. 274, 31763?31766 (1999).

    Article  CAS  PubMed  Google Scholar 

  33. Wagner, J. et al. The dinB gene encodes a novel E. coli DNA polymerase, DNA Pol IV, involved in mutagenesis. Mol. Cell 4, 281?286 (1999).

    Article  CAS  PubMed  Google Scholar 

  34. Ohmori, H. et al. The Y-family of DNA polymerases. Mol. Cell 8, 7?8 (2001).

    Article  CAS  PubMed  Google Scholar 

  35. Byrnes, J. J., Downey, K. M., Black, V. L. & So, A. G. A new mammalian DNA polymerase with 3′ to 5′ exonuclease activity: DNA polymerase δ. Biochemistry 15, 2817?2823 (1976).

    Article  CAS  PubMed  Google Scholar 

  36. Bolden, A., Noy, G. P. & Weissbach, A. DNA polymerase of mitochondria is a γ polymerase. J. Biol. Chem. 252, 3351?3356 (1977).

    CAS  PubMed  Google Scholar 

  37. Focher, F. et al. Calf thymus DNA polymerase δ independent of proliferating cell nuclear antigen. Nucleic Acids Res. 17, 1805?1821 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Morrison, A. et al. REV3, a Saccharomyces cerevisiae gene whose function is required for induced mutagenesis, is predicted to encode a nonessential DNA polymerase. J. Bacteriol. 171, 5659?5667 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Nelson, J. R., Lawrence, C. W. & Hinkle, D. C. Deoxynucleotidyl transferase activity of yeast REV1 protein. Nature 382, 729?731 (1996).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

I apologize for the necessarily restricted listing of references concerning mammalian DNA polymerases. I thank L. Loeb, M. DePamphilis, U. Hubscher, T. Kunkel, S. Wilson and D. Bogenhagen for helpful discussions, and L. McDaniel and N. Kosarek for careful reading of the manuscript.

Author information

Authors and Affiliations

  1. the Department of Pathology, Laboratory of Molecular Pathology, University of Texas Southwestern Medical Center, Dallas, 79503-9072, Texas, USA

    Errol C. Friedberg

Authors
  1. Errol C. Friedberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

The author declares no competing financial interests.

Related links

Related links

FURTHER INFORMATION

Errol Friedberg's laboratory

Rights and permissions

Reprints and permissions

About this article

Cite this article

Friedberg, E. The eureka enzyme: the discovery of DNA polymerase. Nat Rev Mol Cell Biol 7, 143–147 (2006). https://doi.org/10.1038/nrm1787

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm1787

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing