DNA topoisomerases: Structure, function, and mechanism

DNA topoisomerases solve the topological problems associated with DNA repli cation, transcription, recombination, and chromatin remodeling by introduci ng temporary single- or double-strand breaks in the DNA. In addition, these enzymes fine-tune the steady-state level of DNA supercoiling both to facil itate protein interactions with the DNA and to prevent excessive supercoili ng that is deleterious. In recent years, the crystal structures of a number of topoisomerase fragments, representing nearly all the known classes of e nzymes, have been solved. These structures provide remarkable insights into the mechanisms of these enzymes and complement previous conclusions based on biochemical analyses. Surprisingly, despite little or no sequence homolo gy, both type IA and type ITA topoisomerases from prokaryotes and the type IIA enzymes from eukaryotes share structural folds that appear to reflect f unctional motifs within critical regions of the enzymes. The type IB enzyme s are structurally distinct from all other known topoisomerases but are sim ilar to a class of enzymes referred to as tyrosine recombinases. The struct ural themes common to all topoisomerases include hinged clamps that open an d close to bind DNA, the presence of DNA binding cavities for temporary sto rage of DNA segments, and the coupling of protein conformational changes to DNA rotation or DNA movement. For the type II topoisomerases, the binding and hydrolysis of ATP further modulate conformational changes in the enzyme s to effect changes in DNA topology.