Energy coupling in type II topoisomerases: why do they hydrolyze ATP?

Abstract

Type II topoisomerases are essential enzymes in all cells. They help to solve the topological problems of DNA by passing one double helix through a transient break in another, in a reaction coupled to the hydrolysis of ATP. Members of one class of the enzymes, DNA gyrases, are configured to carry out an intramolecular reaction, removing positive supercoiling and introducing negative supercoiling into circular DNA using free energy derived from ATP hydrolysis. The nonsupercoiling class, including bacterial topoisomerase IV and eukaryotic topoisomerase II enzymes, can carry out both intra- and intermolecular reactions, and their primary role is the unlinking (decatenation) of daughter replicons before partition. In these enzymes, ATP hydrolysis is coupled to a reduction in DNA complexity (catenation, supercoiling, and knotting) below the level expected at equilibrium. This review discusses our current understanding of the mechanisms behind the coupling of the energy of ATP hydrolysis to topological changes catalyzed by both of these classes of enzyme.