Type II Topoisomerase - Topology Simplification

Topology Simplification

Type IIA topoisomerases are essential in the separation of entangled daughter strands during replication. This function is believed to be performed by topoisomerase II in eukaryotes and by topoisomerase IV in prokaryotes. Failure to separate these strands leads to cell death. Type IIA topoisomerases have the special ability to relax DNA to a state below that of thermodynamic equilibrium, a feature unlike type IA, IB, and IIB topoisomerases. This ability, known as topology simplification, was first identified by Rybenkov et al. (Science 1997). The hydrolysis of ATP drives this simplification, but a clear molecular mechanism for this simplification is still lacking. Several models to explain this phenomenon have been proposed, including two models that rely on the ability of type IIA topoisomerases to recognize bent DNA duplexes (Vologodskiy, Proceedings of the National Academy of Science 1999). Biochemistry, electron microscopy, and recent structures of topoisomerase II bound to DNA reveal that type IIA topoisomerases bind at the apices of DNA, supporting this model.