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Left-handed helical conformation of poly[d(A-m5C) · d(G-T)]

Nature volume 304, pages 83–86 (1983)Cite this article

Abstract

Poly[d(G-C)] serves as the prototype for the right-to-left (B to Z) transition in the helical sense of DNA, both in solution1 and in the crystal form2,3. However, the question remains as to which other synthetic and natural DNAs have the potential to adopt left-handed conformations. One logical candidate is the canonical alternating purine–pyrimidine sequence d(A-C)n · d(G-T)n which seems to be widely disseminated in eukaryotic genomes4,5. Our approach to this question is based on the enzymatic synthesis of poly[d(A-C) · d(G-U)] derivatives with systematic methyl and halogen substitutions in the C-5 position of the pyrimidines C and U. Such modifications in poly[d(G-C)] have previously been shown to potentiate the B to Z transition6,7. Here we report a highly cooperative, reversible, salt- and temperature-dependent transition for poly[d(A-m5C) · d(G-T)], a repeat of the d(A-m5C) sequence which may occur in natural DNA8. Spectroscopic studies and the demonstrated ability to bind anti-Z-DNA antibodies suggest that the new helical conformation is left-handed and shares structural features with known Z-DNA. However, a novel property, not exhibited by poly[d(G-C)]1, is the profound temperature dependence of the conformational equilibrium.

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References

  1. Pohl, F. M. & Jovin, T. M. J. molec. Biol. 67, 375–396 (1972).

    Article  CAS  Google Scholar 

  2. Drew, H. R. & Dickerson, R. E. J. molec. Biol. 152, 723–736 (1981).

    Article  CAS  Google Scholar 

  3. Wang, A. H.-J. et al. Science 211, 171–176 (1981).

    Article  ADS  CAS  Google Scholar 

  4. Hamada, H. & Kakunaga, T. Nature 298, 396–398 (1982).

    Article  ADS  CAS  Google Scholar 

  5. Hamada, H., Petrino, M. G. & Kakunaga, T. Proc. natn. Acad. Sci. U.S.A. 79, 6465–6469 (1982).

    Article  ADS  CAS  Google Scholar 

  6. Behe, M. & Felsenfeld, G. Proc. natn. Acad. Sci. U.S.A. 78, 1619–1623 (1981).

    Article  ADS  CAS  Google Scholar 

  7. Malfoy, B., Rousseau, N. & Leng, M. Biochemistry 21, 5463–5467 (1982).

    Article  CAS  Google Scholar 

  8. Adams, R. L. P. & Burdon, R. H. CRC crit. Rev. Biochem. 13, 349–384 (1982).

    Article  CAS  Google Scholar 

  9. Jovin, T. M. et al. Cold Spring Harb. Symp. quant. Biol. 47, 143–154 (1983).

    Article  Google Scholar 

  10. McIntosh, L. P., Zarling, D. A., van de Sande, J. H. & Jovin, T. M. J. molec. Biol. (submitted).

  11. van de Sande, J. H. & Jovin, T. M. EMBO J. 1, 115–120 (1982).

    Article  CAS  Google Scholar 

  12. van de Sande, J. H., McIntosh, L. P. & Jovin, T. M. EMBO J. 1, 777–785 (1982).

    Article  CAS  Google Scholar 

  13. Patel, D.J., Canuel, L.L. & Pohl, F.M. Proc. natn. Acad. Sci. U.S.A. 76, 2508–2511 (1979).

    Article  ADS  CAS  Google Scholar 

  14. Pohl, F. M., Renade, A. & Stockburger, M. Biochim. biophys. Acta 335, 85–92 (1973).

    Article  Google Scholar 

  15. Thamann, T. J., Lord, R. C., Wang, A. H. J. & Rich, A. Nucleic Acids Res. 9, 5443–5456 (1981).

    Article  CAS  Google Scholar 

  16. Klug, A. et al. J. molec. Biol. 313, 669–680 (1979).

    Article  Google Scholar 

  17. Eckstein, F. & Jovin, T. M. Biochemistry (in the press).

  18. Zimmerman, S. B. A. Rev. Biochem. 51, 395–427 (1982).

    Article  CAS  Google Scholar 

  19. Cohen, J. S., Wooten, J. B. & Chatterjee, C. L. Biochemistry 20, 3049–3055 (1981).

    Article  CAS  Google Scholar 

  20. Patel, D. J., Kozlowski, S. A., Nordheim, A. & Rich, A. Proc. natn. Acad. Sci. U.S.A. 79, 1413–1417 (1982).

    Article  ADS  CAS  Google Scholar 

  21. Hartmann, B. et al. Nucleic Acids Res. 10, 3261–3277 (1982).

    Article  CAS  Google Scholar 

  22. Brahms, S. et al. J. molec. Biol. 162, 473–493 (1982).

    Article  CAS  Google Scholar 

  23. Thomas, G. A. & Peticolas, W. A. J. Am. chem. Soc. (in the press).

  24. Lafer, E. M., Möller A., Nordheim, A., Stollar, B. D. & Rich, A. Proc. natn. Acad. Sci. U.S.A. 78, 3546–3550 (1981).

    Article  ADS  CAS  Google Scholar 

  25. Zarling, D. A. et al. J. molec. Biol. (submitted).

  26. Nordheim, A. et al. Cell 31, 309–318 (1982).

    Article  CAS  Google Scholar 

  27. Miller, F. et al. EMBO J. (submitted).

  28. Nordheim, A. & Rich, A. Proc. natn. Acad. Sci. U.S.A. 80, 1821–1825 (1983).

    Article  ADS  CAS  Google Scholar 

  29. Pohl, F. M. in Mobility and Recognition in Cell Biology (eds Sund, H. & Veeger, C.) 267–279 (de Gruyter, Berlin, 1983).

    Book  Google Scholar 

  30. Wang, J. C., Peck, L. J. & Becherer, K. Cold Spring Harb. Symp. quant. Biol. 47 (in the press).

  31. Peck, L. J., Nordheim, A., Rich, A. & Wang, J. C. Proc. natn. Acad. Sci. U.S.A. 79, 4560–4564 (1982).

    Article  ADS  CAS  Google Scholar 

  32. Pohl, F. M., Thomae, R. & DiCapua, E. Nature 300, 545–546 (1982).

    Article  ADS  CAS  Google Scholar 

  33. Lang, M. C., Malfoy, B., Freund, A. M., Duane, M. & Leng, M. EMBO J. 1, 1149–1154 (1982).

    Article  CAS  Google Scholar 

  34. Nordheim, A. et al. Nature 294, 417–422 (1981).

    Article  ADS  CAS  Google Scholar 

  35. Arndt-Jovin, D. et al. Proc. natn. Acad. Sci. U.S.A. (in the press).

  36. Robert-Nicoud, M., Arndt-Jovin, D. J., Zarling, D. A. & Jovin, T. M. in Mobility and Recognition in Cell Biology (eds Sund, H. & Veeger, C.) 281–290 (de Gruyter, Berlin, 1983).

    Book  Google Scholar 

  37. Lemeumier, F., Derbin, C., Malfroy, B., Leng, M. & Taillander, E. Expl Cell Res. 14, 508–513 (1982).

    Article  Google Scholar 

  38. Haniford, D. B. & Pulleyblank, D. E. Nature 209, 632–634 (1983).

    Article  ADS  Google Scholar 

  39. Arnott, S., Chandrasekaran, R., Birdsall, D. L., Leslie, A. G. W. & Ratcliff, R. L. Nature 283, 743–745 (1980).

    Article  ADS  CAS  Google Scholar 

  40. Leslie, A. G. W., Arnott, S., Chandrasekaran, R. & Ratcliff, R. L. J. molec. Biol. 143, 49–72 (1980).

    Article  CAS  Google Scholar 

  41. Vorličková, M., Kypr, J., Kleinwächter, V. & Palecek, E. Nucleic Acids Res. 10, 1071–1080 (1982).

    Article  Google Scholar 

  42. Zimmer, C., Tymen, S., Marck, C. & Guschlbauer, W. Nucleic Acids Res. 10, 1081–1091 (1982).

    Article  CAS  Google Scholar 

  43. Wells, R. D. et al. J. biol. Chem. 257, 10166–10171 (1982).

    CAS  PubMed  Google Scholar 

  44. Nordheim A. et al. Proc. natn. Acad. Sci. U.S.A. 79, 7729–7733 (1982).

    Article  ADS  CAS  Google Scholar 

  45. Gill, J. E., Mazrimas, J. A. & Bishop, C. C. Biochim. biophys. Acta 335, 330–348 (1974).

    Article  CAS  Google Scholar 

  46. Pörschke, D. & Jung, M. Nucleic Acids Res. 10, 6163–6176 (1982).

    Article  Google Scholar 

  47. Massig, G., Stockburger, M., Gärtner, Oesterhelt, D. & Towner, P. J. Raman Spectrosc. 12, 287–294 (1982).

    Article  ADS  CAS  Google Scholar 

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Author notes

  1. Fritz Eckstein: Max-Plank-Institut für experimentelle Medizin, Abteilung Chemie, Hermann-Rein-Strasse 3, D-3400 Göttingen, FRG

  2. Johan H. van de Sande: Department of Medical Biochemistry, University of Calgary, Calgary, Alberta, Canada T2N 1N4

Authors and Affiliations

  1. Max-Planck-Institut für biophysikalische Chemie, Abteilung Molekulare Biologie, Postfach 968, D-3400, Göttingen, FRG

    Lawrence P. McIntosh, Iris Grieger, Fritz Eckstein, David A. Zarling, Johan H. van de Sande & Thomas M. Jovin

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  1. Lawrence P. McIntosh
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  2. Iris Grieger
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  4. David A. Zarling
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  5. Johan H. van de Sande
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  6. Thomas M. Jovin
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McIntosh, L., Grieger, I., Eckstein, F. et al. Left-handed helical conformation of poly[d(A-m5C) · d(G-T)]. Nature 304, 83–86 (1983). https://doi.org/10.1038/304083a0

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