Centre for Bacterial Cell Biology

Event Items

CBCB Seminar: Life Without DNA Replication Origins

Date/Time: 4 May 2017, 13.00

Venue: Baddiley-Clark Building, Newcastle University

Host

Dr Henrik Strahl

Speaker

Dr Thorsten Allers, School of Life Sciences, University of Nottingham

Abstract

DNA replication is initiated at specific chromosomal sites called origins, which serve as binding sites for proteins that recruit the replicative enzymes. Replication origins are assumed to be an essential part of the DNA replication apparatus but we have shown that in the archaeon Haloferax volcanii, life without origins is not only possible but highly efficient.

The replication enzymes found in archaea and eukaryotes differ fundamentally from those in bacteria; due to their shared evolutionary history, the former two are highly similar. For example, the archaeo-eukaryotic replicative helicase MCM is distinct to the bacterial replicative helicase DnaB, and the two complexes migrate in different directions on DNA. By contrast, the key enzyme for homologous recombination – known as RecA in bacteria, RadA in archaea and Rad51 in eukaryotes – is conserved in all domains. If homologous recombination is an ancestral process that predates the split between bacteria, archaea and eukaryotes, and the evolution of their different machineries for DNA replication, could it have been used to initiate replication in the last common ancestor?

We have shown that in the archaeon Haloferax volcanii, deletion of all chromosomal origins leads to the initiation of all DNA replication by homologous recombination. Similar results have been obtained with deletion mutants lacking Orc1/Cdc6 replication initiator proteins, which are required for origin firing. Surprisingly, this leads to accelerated growth with no obvious defects, whereas deletion of origins (or initiator protein genes) in yeast or Escherichia coli leads to severe growth impairment. If homologous recombination alone can efficiently initiate the replication of an entire cellular genome, what purpose do replication origins serve and why they have evolved?

All welcome!