Detailed schematic of the type II topoisomerase reaction cycle, showing all of the points where exogenous agents can disrupt function. During its reaction cycle, the topoisomerase initially binds one duplex DNA segment. Following binding, the topoisomerase can then associate with a second duplex DNA segment. ATP binding stimulates cleavage and opening of the first DNA, and passage of the second through the opening. Agents have been identified that interfere with: (1) DNA binding, (2) ATP binding, (3) DNA cleavage, (4) strand passage, (5) religation, and (6) product release. Only a partial list of all inhibitors and poisons is shown.