DNA topoisomerases: structure, function, and mechanism.
DNA topoisomerases solve the topological problems associated with DNA replication, transcription, recombination, and chromatin remodeling by introducing temporary single- or double-strand breaks in the DNA. In addition, these enzymes fine-tune the steady-state level of DNA supercoiling both to facilitate protein interactions with the DNA and to prevent excessive supercoiling that is deleterious. In recent years, the crystal structures of a number of topoisomerase fragments, representing nearly all the known classes of enzymes, 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 homology, both type IA and type IIA topoisomerases from prokaryotes and the type IIA enzymes from eukaryotes share structural folds that appear to reflect functional motifs within critical regions of the enzymes. The type IB enzymes are structurally distinct from all other known topoisomerases but are similar to a class of enzymes referred to as tyrosine recombinases. The structural themes common to all topoisomerases include hinged clamps that open and close to bind DNA, the presence of DNA binding cavities for temporary storage 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 enzymes to effect changes in DNA topology.
Champoux
J J
JJ
Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195-7242, USA. champoux@u.washington.edu
D001105:Archaea / Q000201:enzymology; D001419:Bacteria / Q000201:enzymology; D026942:DNA Topoisomerases / Q000737:chemistry* / Q000502:physiology*; D004264:DNA Topoisomerases, Type I; D006801:Humans; D014615:Vaccinia / Q000201:enzymology; D015003:Yeasts / Q000201:enzymology
D026942:DNA Topoisomerases; D004264:DNA Topoisomerases, Type I