Skip to main content
SpringerLink
Log in

Alteration of ribonucleotide reductase in aphidicolin-resistant mutants of mouse FM3A cells with associated resistance to arabinosyladenine and arabinosylcytosine

  • Published:
Somatic Cell Genetics

Abstract

Aphidicolin-resistant mutants of mouse FM3A cells were isolated and characterized. Most of the mutants were of a type showing associated resistance to arabinosyladenine, arabinosylcytosine, deoxyadenosine, and excess thymidine. This phenotype could also be observed in a variant line selected by resistance to a low level of arabinosylcytosine. In cell-cell hybrids, aphidicolin resistance as well as this cross-resistance behaved as codominant traits. The mutants had an increased dATP pool and decreased ability to incorporate labeled deoxycytidine into macromolecules. Genetic and biochemical evidence suggested that the mutation conferring the pleiotropic phenotype resulted from a change in ribonucleotide reductase activity such that the enzyme was desensitized to the allosteric negative effector dATP. This alteration of the enzyme could account for the marked change in deoxynucleotide pools and for the aphidicolin resistance of the mutants.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Literature cited

  1. Brundet, K.M., Dalziel, W., Hesp, B., Jarvis, J.A., and Neidle, S. (1972).J. Chem. Soc. D. Chem. Commun. 1972:1027–1028.

    Google Scholar 

  2. Bucknall, R.A., Moores, H., Simms, R., and Hesp, B. (1973).Antimicrob. Agents Chemother. 4:294–298.

    PubMed  Google Scholar 

  3. Ikegami, S., Taguchi, T., Ohashi, M., Oguro, M., Nagano, H., and Mano, Y. (1978).Nature 275:458–460.

    PubMed  Google Scholar 

  4. Ohashi, M., Taguchi, T., and Ikegami, S. (1978).Biochem. Biophys. Res. Commun. 82:1084–1090.

    PubMed  Google Scholar 

  5. Hanaoka, F., Kato, H., Ikegami, S., Ohashi, M., and Yamada, M. (1979).Biochem. Biophys. Res. Commun. 87:575–580.

    PubMed  Google Scholar 

  6. Pedrali-Noy, G., and Spadari, S. (1979).Biochem. Biophys. Res. Commun. 88:1194–1202.

    PubMed  Google Scholar 

  7. Berger, N.A., Kurohara, K.K., Petzold, S.J., and Sikorski, G.W. (1979).Biochem. Biophys. Res. Commun. 89:218–225.

    PubMed  Google Scholar 

  8. Weissbach, A. (1977).Annu. Rev. Biochem. 46:25–47.

    PubMed  Google Scholar 

  9. Wist, E., and Prydz, H. (1979).Nucl. Acids Res. 6:1583–1590.

    PubMed  Google Scholar 

  10. Longiau, M., Ikeda, J., Jarkovsky, Z., Horwitz, S.B., and Horwitz, M.S. (1979).Nucl. Acids Res. 6:3369–3386.

    PubMed  Google Scholar 

  11. Habara, A., Kano, K., Nagano, H., Mano, Y., Ikegami, S., and Yamashita, T. (1980).Biochem. Biophys. Res. Commun. 92:8–12.

    PubMed  Google Scholar 

  12. Oguro, M., Shioda, M., Nagano, H., Mano, Y., Hanaoka, F., and Yamada, M. (1980).Biochem. Biophys. Res. Commun. 92:13–19.

    PubMed  Google Scholar 

  13. Ayusawa, D., Iwata, K., Kozu, T., Ikegami, S., and Seno, T. (1979).Biochem. Biophys. Res. Commun. 91:946–954.

    PubMed  Google Scholar 

  14. Clements, G.B. (1975).Adv. Cancer Res. 21:273–390.

    PubMed  Google Scholar 

  15. Ayusawa, D., Iwata, K., Ikegami, S., and Seno, T. (1980).Cell Struct. Funct. 5:147–154.

    Google Scholar 

  16. Miller, M.R., Castellot, J.J., and Pardee, A.B. (1978).Biochemistry 17:1073–1080.

    PubMed  Google Scholar 

  17. Oguro, M., Suzuki-Hori, C., Nagano, H., Mano, Y., and Ikegami, S. (1979).Eur. J. Biochem. 97:603–607.

    PubMed  Google Scholar 

  18. Nakano, N. (1966).Tohoku J. Exp. Med. 88:69–84.

    PubMed  Google Scholar 

  19. Ayusawa, D., Koyama, H., Iwata, K., and Seno, T. (1980).Somat. Cell Genet. 6:261–270.

    PubMed  Google Scholar 

  20. Davidson, R.L., O'Mulley, K.O., and Wheeler, T.B. (1976).Somat. Cell Genet. 2:271–280.

    PubMed  Google Scholar 

  21. Lewis, W.H., and Wright, J.A. (1978).J. Cell. Physiol. 97:87–97.

    PubMed  Google Scholar 

  22. Jacobsen, D.W., and Kirchner, J. (1968).Anal. Biochem. 32:474–477.

    Google Scholar 

  23. Reichard, P. (1958).Acta Chem. Scand. 12:2048.

    Google Scholar 

  24. Iwata, K., Ayusawa, D., and Seno, T. (1979).Cell Struct. Funct. 4:317–320.

    Google Scholar 

  25. Skoog, L. (1970).Eur. J. Biochem. 17:202–208.

    PubMed  Google Scholar 

  26. Lindberg, V., and Skoog, L. (1970).Anal. Biochem. 34:152–160.

    PubMed  Google Scholar 

  27. Robert de Saint Vincent, B., and Buttin, G. (1979).Somat. Cell Genet. 5:67–82.

    PubMed  Google Scholar 

  28. Robert de Saint Vincent, B., Déchamps, M., and Buttin, G. (1980).J. Biol. Chem. 255:162–167.

    PubMed  Google Scholar 

  29. Meuth, M., Trudel, M., and Siminovitch, L. (1979).Somat. Cell Genet. 5:303–313.

    Google Scholar 

  30. Plegemann, P.G.W., Marz, R., and Wohlhuefer, R.M. (1978).Cancer Res. 38:978–989.

    PubMed  Google Scholar 

  31. Hauschka, P.V. (1973).Methods Cell Biol. 7:361–462.

    PubMed  Google Scholar 

  32. Thelander, L.,and Reichard, P. (1979).Annu. Rev. Biochem. 48:133–158.

    Google Scholar 

  33. Lewis, W.,and Wright, J.A. (1978).J. Cell. Physiol. 97:73–86.

    PubMed  Google Scholar 

  34. Lewis, W., and Wright, J.A. (1979).Somat. Cell Genet. 5:83–96.

    PubMed  Google Scholar 

  35. Meuth, M.,and Green, H. (1974).Cell 3:367–374.

    PubMed  Google Scholar 

  36. Meuth, M., Aufreiter, E., and Reichard, P. (1976).Eur. J. Biochem. 71:39–43.

    PubMed  Google Scholar 

  37. Mathews, C.K., North, T.W., and Reddy, G.P.V. (1979).Adv. Enzyme Regul. 17:133–156.

    Google Scholar 

  38. Durham, J.P., and Ives, D.H. (1970).J. Biol. Chem. 245:2276–2284.

    PubMed  Google Scholar 

  39. Smets, L.A. (1969).J. Cell. Physiol. 74:63–66.

    PubMed  Google Scholar 

  40. Tattersall, M.H.N., Jackson, R.C., Jackson, S.T.M., and Harrap, K.R. (1974).Eur. J. Cancer 10:819–826.

    PubMed  Google Scholar 

  41. Lowe, J.K., and Grindey, G.D. (1976).Mol. Pharmacol. 12:177–184.

    PubMed  Google Scholar 

  42. Walters, R.A., and Ratliff, R.L. (1975).Biochim. Biophys. Acta 414:221–230.

    PubMed  Google Scholar 

  43. Fox, I.H., and Kelley, W.N. (1978).Annu. Rev. Biochem. 47:655–686.

    Google Scholar 

  44. Wickner, H. (1978).Annu. Rev. Biochem. 47:1163–1191.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Immunology and Virology, Saitama Cancer Center Research Institute, Ina-machi, 362, Saitama-ken, Japan

    D. Ayusawa, K. Iwata & T. Seno

Authors
  1. D. Ayusawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. Iwata
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. Seno
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ayusawa, D., Iwata, K. & Seno, T. Alteration of ribonucleotide reductase in aphidicolin-resistant mutants of mouse FM3A cells with associated resistance to arabinosyladenine and arabinosylcytosine. Somat Cell Mol Genet 7, 27–42 (1981). https://doi.org/10.1007/BF01544746

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01544746

Keywords

Search

Navigation