Quaternary changes in topoisomerase II may direct orthogonal movement of two DNA strands.
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.
Fass
D
D
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02140, USA.
Bogden
C E
CE
Berger
J M
JM
D001665:Binding Sites; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D009068:Movement; D011487:Protein Conformation
D004247:DNA; D004250:DNA Topoisomerases, Type II