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.

  • Review Article
  • Published:

Functional inactivation of genes by dominant negative mutations

Abstract

Molecular biologists are increasingly faced with the problem of assigning a function to genes that have been cloned. A new approach to this problem involves the manipulation of the cloned gene to create what are known as 'dominant negative' mutations. These encode mutant polypeptides that when overexpressed disrupt the activity of the wild-type gene. There are many precedents for this kind of behaviour in the literature—some oncogenes might be examples of naturally occurring dominant negative mutations.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Similar content being viewed by others

References

  1. Rebagliati, M. R., Weeks, D. L., Harvey, R. P. & Melton, D. A. Cell 42, 769–777 (1985).

    Article  CAS  Google Scholar 

  2. Young, R. A. & Davis, R. W. Proc. natn. Acad. Sci. U.S.A. 80, 1194–1198 (1983).

    Article  ADS  CAS  Google Scholar 

  3. Muller, H. J. in Proceedings of the Sixth International Congress of Genetics (ed. Jones, D.F.) 213–255 (Brooklyn Botanic Gardens, Menasha, Wisconsin, 1932).

    Google Scholar 

  4. Scherer, S. & Davis, R. W. Proc. natn. Acad. Sci. U.S.A. 76, 4951–4955 (1979).

    Article  ADS  CAS  Google Scholar 

  5. Rothstein, R. J. Meth. Enzym. 101, 202–211 (1983).

    Article  CAS  Google Scholar 

  6. Russell, P. & Nurse, P. Cell 45, 145–153 (1986).

    Article  CAS  Google Scholar 

  7. Miller, B. L., Miller, K. Y. & Timberlake, W. E. Molec. cell. Biol. 5, 1714–1721 (1985).

    Article  CAS  Google Scholar 

  8. May, G. S., Weatherbee, J. A., Gambino, J., Tsang, M. L.-S. & Morris, N. R. in Molecular Genetics of Filamentous Fungi (ed. Timberlake, W. E.) 239–251 (Liss, New York, 1985).

    Google Scholar 

  9. Smithies, O., Gregg, R. G., Boggs, S. S., Koralewski, M. A. & Kucherlapati, R. S. Nature 317, 230–234 (1985).

    Article  ADS  CAS  Google Scholar 

  10. Thomas, K. R. & Capecchi, M. R. Nature 324, 34–38 (1986).

    Article  ADS  CAS  Google Scholar 

  11. Izant, J. G. & Weintraub, H. Cell 36, 1007–1015 (1984).

    Article  CAS  Google Scholar 

  12. Melton, D. A. Proc. natn. Acad. Sci. U.S.A 82, 144–148 (1985).

    Article  ADS  CAS  Google Scholar 

  13. North, G. Nature 313, 635 (1985).

    Article  ADS  Google Scholar 

  14. Rosenberg, U. B., Preiss, A., Seifert, E., Jäckle, H. & Knipple, D. C. Nature 313, 703–706 (1985).

    Article  ADS  CAS  Google Scholar 

  15. Crowley, T. E., Nellen, W., Gomer, R. H. & Firtel, R. A. Cell 43, 633–641 (1985).

    Article  CAS  Google Scholar 

  16. Nishikura, K. & Murray, J. M. Molec. cell. Biol. 7, 639–649 (1987).

    Article  CAS  Google Scholar 

  17. Kim, S. K. & Wold, B. J. Cell 42, 129–138 (1985).

    Article  CAS  Google Scholar 

  18. Rebagliati, M. R. & Melton, D. A. Cell 48, 599–605 (1987).

    Article  CAS  Google Scholar 

  19. Bass, B. L. & Weintraub, H. Cell 48, 607–613 (1987).

    Article  CAS  Google Scholar 

  20. Meeks-Wagner, D. & Hartwell, L. H. Cell 44, 43–52 (1986).

    Article  CAS  Google Scholar 

  21. Blose, S. H., Meltzer, D. I. & Feramisco, J. R. J. Cell Biol. 98, 847–858 (1984).

    Article  CAS  Google Scholar 

  22. Wehland, J. & Willingham, M. C. J. Cell Biol. 97, 1476–1490 (1983).

    Article  CAS  Google Scholar 

  23. Feramisco, J. R. et al. Nature 314, 639–642 (1985).

    Article  ADS  CAS  Google Scholar 

  24. Kung, H.-F., Smith, M. R., Bekesi, E., Manne, V. & Stacey, D. W. Expl. Cell Res. 162, 363–371 (1986).

    Article  CAS  Google Scholar 

  25. Chandler, V. L., Maler, B. A. & Yamamoto, K. R. Cell 33, 489–499 (1983).

    Article  CAS  Google Scholar 

  26. Swift, G. H., Hammer, R. E., MacDonald, R. J. & Brinster, R. L. Cell 38, 639–646 (1984).

    Article  CAS  Google Scholar 

  27. Miller, J. H. in The Operon (eds Miller, J. H. & Reznikoff, W. S.) 31–88 (Cold Spring Harbor Press, New York, 1978).

    Google Scholar 

  28. Kelley, R. L. & Yanofsky, C. Proc. natn. Acad. Sci. U.S.A. 82, 483–487 (1985).

    Article  ADS  CAS  Google Scholar 

  29. Matthews, B. W., Ohlendorf, D. H., Anderson, W. F. & Takeda, Y. Proc. natn. Acad. Sci. U.S.A. 79, 1428–1432 (1982).

    Article  ADS  CAS  Google Scholar 

  30. Sauer, R. T., Yocum, R. R., Doolittle, R. F., Lewis, M. & Pabo, C. O. Nature 298, 447–451 (1982).

    Article  ADS  CAS  Google Scholar 

  31. Hope, I. A. & Struhl, K. Cell 46, 885–894 (1986).

    Article  CAS  Google Scholar 

  32. Wachsman, W. et al. Science 235, 674–677 (1987).

    Article  ADS  CAS  Google Scholar 

  33. Waterston, R. H., Hirsh, D. & Lane, T. R. J. molec. Biol. 180, 473–496 (1984).

    Article  CAS  Google Scholar 

  34. Fuller, M. T. in Gametogenesis and the Early Embryo (ed. Gall, J. G.) 19–41 (Liss, New York, 1986).

    Google Scholar 

  35. Kusch, M. & Edgar, R. S. Genetics 113, 621–639 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Park, E. C. & Horvitz, H. R. Genetics 113, 821–852 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Alberts, B. M. Cold Spring Harb. Symp. quant. Biol. 49, 1–12 (1984).

    Article  CAS  Google Scholar 

  38. Wente, S. R. & Schachman, H. K. Proc. natn. Acad. Sci. U.S.A. 84, 31–34 (1987).

    Article  ADS  CAS  Google Scholar 

  39. Robey, E. A. & Schachman, H. K. Proc. natn. Acad. Sci. U.S.A. 82, 361–365 (1985).

    Article  ADS  CAS  Google Scholar 

  40. Gibbons, I., Flatgaard, J. E. & Schachman, H. K. Proc. natn. Acad. Sci. U.S.A. 72, 4298–4302 (1975).

    Article  ADS  CAS  Google Scholar 

  41. Mitchell, A. P. Genetics 111, 243–258 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Almassay, R. J., Janson, C. A., Hamlin, R., Xuong, N-H. & Eisenberg, D. Nature 323, 304–309 (1986).

    Article  ADS  Google Scholar 

  43. Johnston, S. A., Zavortink, M. J., Debouck, C. & Hopper, J. E. Proc. natn. Acad. Sci. U.S.A. 83, 6553–6557 (1986).

    Article  ADS  CAS  Google Scholar 

  44. De Lozanne, A. & Spudich, J. A. Science 236, 1086–1091 (1987).

    Article  ADS  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Herskowitz, I. Functional inactivation of genes by dominant negative mutations. Nature 329, 219–222 (1987). https://doi.org/10.1038/329219a0

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/329219a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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