Plenary Talk
James Berger,
Department of Molecular and Cell Biology,
University of California, Berkeley
Understanding a DNA disentangling machine: the structural mechanisms of type II topoisomerases
Discovered over thirty years ago, type II topoisomerases remain one of the more fascinating and enigmatic classes of molecular machines in the cell. Through a distinctive ability to transport one DNA duplex through another, these enzymes play an integral part in maintaining genome topology and the error-free separation of newly-replicated chromosomes. Within a few years after their initial isolation, biochemical studies pinpointed a number of critical functional features — such as the inversion of DNA crossovers and the pumping of DNA through separable enzyme interfaces — that allow type II topoisomerases to disentangle DNA segments. It took nearly twenty years, however, for structural studies to start to reveal the protein mechanics that underlie their strand passage reaction. This survey will cover the the physical insights that led to a relatively unified physical model accounting for type II topoisomerase action. Despite this framework, however, a number of pressing issues still exist, from understanding how type II topoisomerases convert chemical energy into dynamic motion, to how biological variants of these enzymes selectively discriminate between DNA topologies to accommodate specific replicative and transcriptional events.