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 a nd cell viability. The active sites of the type II topoisomerase dimer asso ciate covalently with the DNA break-points and must separate by at least th e width of the second DNA duplex to accommodate transport. A new structure of the Saccharomyces cerevisiae topoisomerase II DNA-binding and cleavage c ore suggests that in addition to conformational changes in the DNA-opening platform, a dramatic reorganization of accessory domains may occur during c atalysis. These conformational differences have implications for both the D NA-breaking and duplex-transport events in the topo II reaction mechanism, suggest a mechanism by which two distinct drug-resistance loci interact, an d illustrate the scope of structural changes in the cycling of molecular ma chines.