Figure 3.

Schematic mechanism for the relaxation of DNA supercoils by human topoisomerase I which incorporates a semiopen configuration of the protein. Protein is represented in Pac-Man-like form with upper cap and lower base (in green) connected by a springlike hinge. (Yellow) DNA downstream of the cut; (red) DNA upstream of it. Note that positive supercoil relaxation is showcased here. For the relaxation of negative supercoils, the overall mechanism remains the same; however, the transition and semiopen states are replaced by configurations in which the hinge is opened as opposed to the lips, and the free energy profiles are distinct (see text).