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Quaternary changes in topoisomerase II may direct orthogonal movement of two DNA strands

Nature Structural Biology volume 6, pages 322–326 (1999)Cite this article

Abstract

Type II DNA topoisomerases mediate the passage of one DNA duplex through a transient break in another, an event essential for chromosome segregation and cell viability. The active sites of the type II topoisomerase dimer associate covalently with the DNA break-points and must separate by at least the width of the second DNA duplex to accommodate transport. A new structure of the Saccharomyces cerevisiae topoisomerase II DNA-binding and cleavage core suggests that in addition to conformational changes in the DNA-opening platform, a dramatic reorganization of accessory domains may occur during catalysis. These conformational differences have implications for both the DNA-breaking and duplex-transport events in the topo II reaction mechanism, suggest a mechanism by which two distinct drug-resistance loci interact, and illustrate the scope of structural changes in the cycling of molecular machines.

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Figure 1: Type II topoisomerase structure and a new quaternary arrangement of yeast topo II.
Figure 2: Opening and closing of the topo II A' heads.
Figure 3: Stereo diagrams of the B' domains, and side views in the context of the topo II DNA-binding and cleavage core.
Figure 4: Schematic illustration of a proposed B' domain rotation within the global catalytic mechanism.

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Acknowledgements

We thank J.E. Lindsley, A.S. Lynch, P.S. Kim, S.J. Gamblin, S.C. Harrison, and J.C. Wang for discussions on topoisomerase mechanism. We are grateful to C. Ogata of the Brookhaven National Synchrotron Light Source beamline X4A and members of the laboratory of P.S.K. for assistance with data collection, and to S.C.H., J.C.W., D. Minor and M.D. Nichols for critical reading of the manuscript. The authors thank A. Maxwell and R.C. Liddington for providing coordinates of the GyrA breakage-reunion domain, and D.B. Wigley for providing coordinates of the GyrB ATPase domain. D.F. is supported by an NIH Grant to P.S. Kim. J.M.B. acknowledges support from the W.M. Keck Foundation and the Whitehead Institute.

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  1. Deborah Fass

    Present address: Department of Structural Biology, Weizmann Institute of Science, Rehovot, 76100, Israel

Authors and Affiliations

  1. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, 02140, Massachusetts, USA

    Deborah Fass & Cynthia E. Bogden

  2. Department of Molecular and Cell Biology, 229 Stanley Hall #3206 University of California, Berkeley, Berkeley, 94720, California, USA

    James M. Berger

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  1. Deborah Fass
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Correspondence to James M. Berger.

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Fass, D., Bogden, C. & Berger, J. Quaternary changes in topoisomerase II may direct orthogonal movement of two DNA strands. Nat Struct Mol Biol 6, 322–326 (1999). https://doi.org/10.1038/7556

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