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Somatic Cell Genetics

, Volume 7, Issue 1, pp 27–42 | Cite as

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

  • D. Ayusawa
  • K. Iwata
  • T. Seno
Article

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.

Keywords

Macromolecule Thymidine Reductase Activity Marked Change Biochemical Evidence 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Literature cited

  1. 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. 2.
    Bucknall, R.A., Moores, H., Simms, R., and Hesp, B. (1973).Antimicrob. Agents Chemother. 4:294–298.PubMedGoogle Scholar
  3. 3.
    Ikegami, S., Taguchi, T., Ohashi, M., Oguro, M., Nagano, H., and Mano, Y. (1978).Nature 275:458–460.PubMedGoogle Scholar
  4. 4.
    Ohashi, M., Taguchi, T., and Ikegami, S. (1978).Biochem. Biophys. Res. Commun. 82:1084–1090.PubMedGoogle Scholar
  5. 5.
    Hanaoka, F., Kato, H., Ikegami, S., Ohashi, M., and Yamada, M. (1979).Biochem. Biophys. Res. Commun. 87:575–580.PubMedGoogle Scholar
  6. 6.
    Pedrali-Noy, G., and Spadari, S. (1979).Biochem. Biophys. Res. Commun. 88:1194–1202.PubMedGoogle Scholar
  7. 7.
    Berger, N.A., Kurohara, K.K., Petzold, S.J., and Sikorski, G.W. (1979).Biochem. Biophys. Res. Commun. 89:218–225.PubMedGoogle Scholar
  8. 8.
    Weissbach, A. (1977).Annu. Rev. Biochem. 46:25–47.PubMedGoogle Scholar
  9. 9.
    Wist, E., and Prydz, H. (1979).Nucl. Acids Res. 6:1583–1590.PubMedGoogle Scholar
  10. 10.
    Longiau, M., Ikeda, J., Jarkovsky, Z., Horwitz, S.B., and Horwitz, M.S. (1979).Nucl. Acids Res. 6:3369–3386.PubMedGoogle Scholar
  11. 11.
    Habara, A., Kano, K., Nagano, H., Mano, Y., Ikegami, S., and Yamashita, T. (1980).Biochem. Biophys. Res. Commun. 92:8–12.PubMedGoogle Scholar
  12. 12.
    Oguro, M., Shioda, M., Nagano, H., Mano, Y., Hanaoka, F., and Yamada, M. (1980).Biochem. Biophys. Res. Commun. 92:13–19.PubMedGoogle Scholar
  13. 13.
    Ayusawa, D., Iwata, K., Kozu, T., Ikegami, S., and Seno, T. (1979).Biochem. Biophys. Res. Commun. 91:946–954.PubMedGoogle Scholar
  14. 14.
    Clements, G.B. (1975).Adv. Cancer Res. 21:273–390.PubMedGoogle Scholar
  15. 15.
    Ayusawa, D., Iwata, K., Ikegami, S., and Seno, T. (1980).Cell Struct. Funct. 5:147–154.Google Scholar
  16. 16.
    Miller, M.R., Castellot, J.J., and Pardee, A.B. (1978).Biochemistry 17:1073–1080.PubMedGoogle Scholar
  17. 17.
    Oguro, M., Suzuki-Hori, C., Nagano, H., Mano, Y., and Ikegami, S. (1979).Eur. J. Biochem. 97:603–607.PubMedGoogle Scholar
  18. 18.
    Nakano, N. (1966).Tohoku J. Exp. Med. 88:69–84.PubMedGoogle Scholar
  19. 19.
    Ayusawa, D., Koyama, H., Iwata, K., and Seno, T. (1980).Somat. Cell Genet. 6:261–270.PubMedGoogle Scholar
  20. 20.
    Davidson, R.L., O'Mulley, K.O., and Wheeler, T.B. (1976).Somat. Cell Genet. 2:271–280.PubMedGoogle Scholar
  21. 21.
    Lewis, W.H., and Wright, J.A. (1978).J. Cell. Physiol. 97:87–97.PubMedGoogle Scholar
  22. 22.
    Jacobsen, D.W., and Kirchner, J. (1968).Anal. Biochem. 32:474–477.Google Scholar
  23. 23.
    Reichard, P. (1958).Acta Chem. Scand. 12:2048.Google Scholar
  24. 24.
    Iwata, K., Ayusawa, D., and Seno, T. (1979).Cell Struct. Funct. 4:317–320.Google Scholar
  25. 25.
    Skoog, L. (1970).Eur. J. Biochem. 17:202–208.PubMedGoogle Scholar
  26. 26.
    Lindberg, V., and Skoog, L. (1970).Anal. Biochem. 34:152–160.PubMedGoogle Scholar
  27. 27.
    Robert de Saint Vincent, B., and Buttin, G. (1979).Somat. Cell Genet. 5:67–82.PubMedGoogle Scholar
  28. 28.
    Robert de Saint Vincent, B., Déchamps, M., and Buttin, G. (1980).J. Biol. Chem. 255:162–167.PubMedGoogle Scholar
  29. 29.
    Meuth, M., Trudel, M., and Siminovitch, L. (1979).Somat. Cell Genet. 5:303–313.Google Scholar
  30. 30.
    Plegemann, P.G.W., Marz, R., and Wohlhuefer, R.M. (1978).Cancer Res. 38:978–989.PubMedGoogle Scholar
  31. 31.
    Hauschka, P.V. (1973).Methods Cell Biol. 7:361–462.PubMedGoogle Scholar
  32. 32.
    Thelander, L.,and Reichard, P. (1979).Annu. Rev. Biochem. 48:133–158.Google Scholar
  33. 33.
    Lewis, W.,and Wright, J.A. (1978).J. Cell. Physiol. 97:73–86.PubMedGoogle Scholar
  34. 34.
    Lewis, W., and Wright, J.A. (1979).Somat. Cell Genet. 5:83–96.PubMedGoogle Scholar
  35. 35.
    Meuth, M.,and Green, H. (1974).Cell 3:367–374.PubMedGoogle Scholar
  36. 36.
    Meuth, M., Aufreiter, E., and Reichard, P. (1976).Eur. J. Biochem. 71:39–43.PubMedGoogle Scholar
  37. 37.
    Mathews, C.K., North, T.W., and Reddy, G.P.V. (1979).Adv. Enzyme Regul. 17:133–156.Google Scholar
  38. 38.
    Durham, J.P., and Ives, D.H. (1970).J. Biol. Chem. 245:2276–2284.PubMedGoogle Scholar
  39. 39.
    Smets, L.A. (1969).J. Cell. Physiol. 74:63–66.PubMedGoogle Scholar
  40. 40.
    Tattersall, M.H.N., Jackson, R.C., Jackson, S.T.M., and Harrap, K.R. (1974).Eur. J. Cancer 10:819–826.PubMedGoogle Scholar
  41. 41.
    Lowe, J.K., and Grindey, G.D. (1976).Mol. Pharmacol. 12:177–184.PubMedGoogle Scholar
  42. 42.
    Walters, R.A., and Ratliff, R.L. (1975).Biochim. Biophys. Acta 414:221–230.PubMedGoogle Scholar
  43. 43.
    Fox, I.H., and Kelley, W.N. (1978).Annu. Rev. Biochem. 47:655–686.Google Scholar
  44. 44.
    Wickner, H. (1978).Annu. Rev. Biochem. 47:1163–1191.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1981

Authors and Affiliations

  • D. Ayusawa
    • 1
  • K. Iwata
    • 1
  • T. Seno
    • 1
  1. 1.Department of Immunology and VirologySaitama Cancer Center Research InstituteSaitama-kenJapan

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