Life Without DNA Replication Origins

DNA replication is initiated at chromosomal sites called origins. Replication origins and the initiator proteins that bind them are assumed to be essential, but we have shown that in Haloferax volcanii, life without origins is not only possible but efficient. The DNA replication enzymes found in archaea and eukaryotes differ fundamentally from those in bacteria, but the key enzyme for homologous recombination –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 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?


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