The Bacterial Replisome: Design Principles for a Dynamic Molecular Machine

Speaker: Professor Nick Dixon, University of Wollongong, Australia

Host: Professor Anders Løbner-Olesen, Functional Genomics, BIO-UCPH

Abstract
The bacterial replisome is a complex and dynamic assembly of more than 20 protein subunits that include the multi-protein Pol III chromosomal replicase and the primosome (helicase/primase). The replisome works on double-stranded DNA to achieve simultaneous copying of both strands at a replication fork at rates that approach 1000 bp/s, with near-perfect fidelity. In the textbook view, leading and lagging strand DNA replication are perfectly coordinated processes that are orchestrated to occur deterministically in discrete steps in space and time. However, there is no evolutionary pressure to achieve such elegance, nor do fundamental chemical principles allow it. I will integrate some recent structural and single-molecule biophysical studies that are being used to develop a new picture of replisomal function that is messier than the textbook view.

Biography
Nick Dixon is Professor of Biological Chemistry and Director, Centre for Medical and Molecular Bioscience at the University of Wollongong, where he has worked since 2006. He was an Australian Research Council Professorial Fellow in 2008–12. He was trained in Biochemistry at the University of Queensland, and had postdoctoral positions at the Australian National University (ANU, Canberra) and Stanford University (Australian NHMRC C.J. Martin and Fulbright Fellowships) before returning to the John Curtin School of Medical Research at ANU as a Queen Elizabeth II Fellow. He established his independent research group at the Research School of Chemistry, ANU in 1986. His major research focus over the past 36 years has been to use the bacterial DNA replication apparatus as a model system to uncover the basic operating principles of Nature’s dynamic multiprotein machines.