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Structure and mechanism of DNA topoisomerase II

An Erratum to this article was published on 14 March 1996

Abstract

The crystal structure of a large fragment of yeast type II DNA topoisomerase reveals a heart-shaped dimeric protein with a large central hole. It provides a molecular model of the enzyme as an ATP-modulated clamp with two sets of jaws at opposite ends, connected by multiple joints. An enzyme with bound DNA can admit a second DNA duplex through one set of jaws, transport it through the cleaved first duplex, and expel it through the other set of jaws.

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References

  1. Gellert, M. A. Rev. Biochem. 50, 879–910 (1981).

    Article  CAS  Google Scholar 

  2. Wang, J. C. A. Rev. Biochem. 54, 665–697 (1985).

    Article  CAS  Google Scholar 

  3. Hsieh, T. in DNA Topology and its Biological Implications (eds Cozzarelli, N. R. & Wang, J. C.) 243–263 (Cold Spring Harbor Laboratory Press, New York, 1990).

    Google Scholar 

  4. Yanagida, M. & Sternglanz, R. in DNA Topology and its Biological Implications (eds Cozzarelli, N. R. & Wang, J. C.) 299–320 (Cold Spring Harbor Laboratory Press, New York, 1990).

    Google Scholar 

  5. Lynn, R., Giaever, G., Swanberg, S. L. & Wang, J. C. Science 233, 647–649 (1986).

    Article  ADS  CAS  Google Scholar 

  6. Uemura, T. & Yanagida, M. EMBO J. 5, 1003–1010 (1986).

    Article  CAS  Google Scholar 

  7. Wyckoff, E., Natalie, D., Nolan, J. M., Lee, M. & Hseih, T. J. molec. Biol. 205, 1–14 (1989).

    Article  CAS  Google Scholar 

  8. Huang, W. M. in Advances in Pharmacology (ed. Liu, L. F.) 201–225 (Academic, San Diego, 1994).

    Google Scholar 

  9. Brown, P. O. & Cozzarelli, N. R. Science 206, 1081–1083 (1979).

    Article  ADS  CAS  Google Scholar 

  10. Liu, L. F., Liu, C. C. & Alberts, B. M. Cell 19, 697–707 (1980).

    Article  CAS  Google Scholar 

  11. Gellert, M., Fisher, L. M., Ohmori, H., O'Dea, M. H. & Mizuuchi, K. Cold Spring Harb. Symp. quant. Biol. 45, 391–398 (1981).

    Article  CAS  Google Scholar 

  12. Sugino, A., Higgins, N. P., Brown, P. O., Peebles, C. L. & Cozzarelli, N. R. Proc. natn. Acad. Sci. U.S.A. 75, 4838–4842 (1978).

    Article  ADS  CAS  Google Scholar 

  13. Adachi, T., Mizuuchi, K., Menzel, R. & Gellert, M. Nucleic Acids Res. 12, 6389–6395 (1984).

    Article  CAS  Google Scholar 

  14. Brown, P. O., Peebles, C. L. & Cozzarelli, N. R. Proc. natn. Acad. Sci. U.S.A. 76, 6110–6114 (1979).

    Article  ADS  CAS  Google Scholar 

  15. Gellert, M., Fisher, L. M. & O'Dea, M. H. Proc. natn. Acad. Sci. U.S.A. 76, 6289–6293 (1979).

    Article  ADS  CAS  Google Scholar 

  16. Wigley, D. B., Davies, G. J., Dodson, E. J., Maxwell, A. & Dodson, G. Nature 351, 624–629 (1991).

    Article  ADS  CAS  Google Scholar 

  17. Ali, J. A., Orphanides, G. & Maxwell, A. Biochemistry 34, 9801–9808 (1995).

    Article  CAS  Google Scholar 

  18. Lindsley, J. E. & Wang, J. C. Proc. natn. Acad. Sci. U.S.A. 88, 10485–10489 (1991).

    Article  ADS  CAS  Google Scholar 

  19. Osheroff, N. J. biol. Chem. 261, 9944–9950 (1986).

    CAS  PubMed  Google Scholar 

  20. Roca, J. R. & Wang, J. C. Cell 71, 833–840 (1992).

    Article  CAS  Google Scholar 

  21. Linsdey, J. E. & Wang, J. C. Nature 361, 749–750 (1993).

    Article  ADS  Google Scholar 

  22. Roca, J. & Wang, J. C. Cell 77, 609–616 (1994).

    Article  CAS  Google Scholar 

  23. Lima, C. D., Wang, J. C. & Mondragón, A. Nature 367, 138–145 (1994).

    Article  ADS  CAS  Google Scholar 

  24. Schultz, S. C., Shields, G. C. & Steitz, T. A. Science 253, 1001–1007 (1991).

    Article  ADS  CAS  Google Scholar 

  25. Ramakrishnan, V., Finch, J. T., Graziano, V., Lee, P. L. & Sweet, R. M. Nature 362, 219–223 (1993).

    Article  ADS  CAS  Google Scholar 

  26. Worland, S. T. & Wang, J. C. J. biol. Chem. 264, 4412–4416 (1989).

    CAS  PubMed  Google Scholar 

  27. Thomas, W., Spell, R. M., Ming, M. E. & Holm, C. Genetics 128, 703–716 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Bernerd, P. & Couturier, M. J. molec. Biol. 226, 735–745 (1992).

    Article  Google Scholar 

  29. Yoshida, H., Bogaki, M., Nakamura, M. & Nakamura, S. Antimicrob. Agents Chemother. 34, 1271–1272 (1990).

    Article  CAS  Google Scholar 

  30. Lee, M. P., Sauder, M. & Hsieh, T. J. biol. Chem. 264, 21779–21787 (1989).

    CAS  PubMed  Google Scholar 

  31. Kirchhausen, T., Wang, J. C. & Harrison, S. C. Cell 41, 933–943 (1985).

    Article  CAS  Google Scholar 

  32. Sander, M. & Hsieh, T. J. biol. Chem. 258, 8421–8428 (1983).

    CAS  PubMed  Google Scholar 

  33. Murzin, A. Curr. Opin. Struct. Biol. 4, 441–449 (1994).

    Article  CAS  Google Scholar 

  34. Otwinowski, Z. & Minor, W. in Data Collection and Processing (eds Sawyer, L., Isaacs, N. & Bailey, S.) 556–562 (SERC Daresbury Laboratory, Warrington, 1993).

    Google Scholar 

  35. Collaborative Computational Project, No. 4 Acta crystallogr. D50, 760–763 (1994).

  36. Cowtan, K. A CCP4 Density Modification Package (The CCP4 Suite of Programs, 1994).

    Google Scholar 

  37. Brünger, A. T. XPLOR (Version 3.1): A System for X-ray Crystallography and NMR (Yale Univ. Press, 1993).

    Google Scholar 

  38. Brünger, A. T. Nature 355, 472–475 (1992).

    Article  ADS  Google Scholar 

  39. Brünger, A. T. A. Rev. phys. Chem. 42, 197–223 (1991).

    Article  ADS  Google Scholar 

  40. Kraulis, P. J. appl. Crystallogr. 24, 924–950 (1991).

    Article  Google Scholar 

  41. Caron, P. & Wang, J. C. Advances in Pharmacology (ed. Liu, L. F.) 271–297 (Academic, San Diego, 1994).

    Google Scholar 

  42. Carson, M. J. molec. Graphics 5, 103–106 (1987).

    Article  CAS  Google Scholar 

  43. Nicholls, A., Sharp, K. A. & Honig, B. H. Proteins Struct. Funct. Genet. 11, 281–296 (1991).

    Article  CAS  Google Scholar 

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Berger, J., Gamblin, S., Harrison, S. et al. Structure and mechanism of DNA topoisomerase II. Nature 379, 225–232 (1996). https://doi.org/10.1038/379225a0

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