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.

  • News & Views
  • Published:

Structural biology

A mechanism for all polymerases

Nature volume 391, pages 231–232 (1998)Cite this article

Access through your institution
Buy or subscribe

Possibly the earliest enzymatic activity to appear in evolution was that of the polynucleotide polymerases — the ability to replicate the genome accurately being a prerequisite for evolution itself. Thus, one might anticipate that the mechanism by which polymerases work would be both simple and universal. Further, these enzymatic scribes must faithfully copy the sequences of the genome into daughter nucleic acid, or the information contained within will be lost for ever. Finally, replicative DNA polymerases are highly processive, traversing the whole genome of a virus DNA without falling off.

On pages 251 and 304 of this issue, Doublié et al.1 and Kiefer et al.2 provide significant insights into the catalytic mechanism, fidelity and processivity of DNA polymerases. In a detailed crystal structure at 2.2 Å resolution, Doublié et al. have captured the DNA polymerase that replicates bacteriophage T7 DNA, along with the Escherichia coli thioredoxin in the act of adding a deoxynucleoside triphosphate (dNTP) to a primer-template DNA. The incoming dNTP (actually dideoxy here) is accompanied by two magnesium ions, which are bound to the phosphates of the nucleotide and to two aspartic-acid residues that are widely conserved among DNA and RNA polymerases. To prevent the reaction from occurring in the crystal, the authors used a dideoxynucleotide at the primer terminus whose 3′ OH, when present, would interact with one of the two metal ions.

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

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

Figure 1: The two-metal-ion mechanism of polynucleotide polymerases3 in the context of the T7 DNA po.

T. ELLENBERGER

Figure 2: Structure of the T7 DNA polymerase, solved by Doublié et al.1, locked in synthesis mode.

References

  1. Doublié, S., Tabor, S., Long, A. M., Richardson, C. C. & Ellenberger, T. Nature 391, 251–258 (1998).

    Article  ADS  Google Scholar 

  2. Kiefer, J. R., Mao, C., Braman, J. C. & Beese, L. S. Nature 391, 304–307 (1998).

    Article  ADS  CAS  Google Scholar 

  3. Steitz, T. A. Curr. Opin. Struct. Biol. 3, 31–38 (1993).

    Google Scholar 

  4. Pelletier, H., Sawaya, M. R., Kumar, A., Wilson, S. H. & Kraut, J. Science 264, 1891–1903 (1994).

    Google Scholar 

  5. Wang, J.et al. Cell 89, 1087–1099 (1997).

    Google Scholar 

  6. Sousa, R., Chung, Y. J., Rose, J. P. & Wang, B. C. Nature 364, 593–599 (1993).

    Article  ADS  CAS  Google Scholar 

  7. Kohlstaedt, L. A., Wang, J., Friedman, J. M., Rice, P. A. & Steitz, T. A. Science 256, 1873–1790 (1992).

    Google Scholar 

  8. Hansen, J. L., Long, A. M. & Schultz, S. C. Structure 5, 1109–1122 (1997).

    Google Scholar 

  9. Eom, S. H., Wang, J. & Steitz, T. A. Nature 382, 278–280 (1996).

    Article  ADS  CAS  Google Scholar 

  10. Jacobo-Molina, A.et al. Proc. Natl Acad. Sci. USA 90, 6320–6324 (1993).

    Google Scholar 

  11. Tabor, S., Huber, H. E. & Richardson, C. C. J. Biol. Chem. 262, 16212–16223 (1987).

    Google Scholar 

  12. Brautigam, C. & Steitz, T. A. Curr. Opin. Struct. Biol. (in the press).

Download references

Author information

Authors and Affiliations

  1. the Department of Molecular Biophysics and Biochemistry, and the Howard Hughes Medical Institute, Yale University, 266 Whitney Avenue, New Haven, 06520-8114, Connecticut, USA

    Thomas A. Steitz

Authors
  1. Thomas A. Steitz
    View author publications

    You can also search for this author inPubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Steitz, T. A mechanism for all polymerases. Nature 391, 231–232 (1998). https://doi.org/10.1038/34542

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/34542

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