Accelerated growth in the absence of DNA replication origins

Hawkins, Michelle, Malla, Sunir, Blythe, Martin J., Nieduszynski, Conrad A. ORCID: and Allers, Thorsten (2013) Accelerated growth in the absence of DNA replication origins. Nature, 503 (7477). pp. 544-547. ISSN 0028-0836

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DNA replication initiates at defined sites called origins, which serve as binding sites for initiator proteins that recruit the replicative machinery. Origins differ in number and structure across the three domains of life and their properties determine the dynamics of chromosome replication. Bacteria and some archaea replicate from single origins, whereas most archaea and all eukaryotes replicate using multiple origins. Initiation mechanisms that rely on homologous recombination operate in some viruses. Here we show that such mechanisms also operate in archaea. We use deep sequencing to study replication in Haloferax volcanii and identify four chromosomal origins of differing activity. Deletion of individual origins results in perturbed replication dynamics and reduced growth. However, a strain lacking all origins has no apparent defects and grows significantly faster than wild type. Origin-less cells initiate replication at dispersed sites rather than at discrete origins and have an absolute requirement for the recombinase RadA, unlike strains lacking individual origins. Our results demonstrate that homologous recombination alone can efficiently initiate the replication of an entire cellular genome. This raises the question of what purpose replication origins serve and why they have evolved.

Item Type: Article
Additional Information: Funding Information: Acknowledgements This work was supported through the Biotechnology and Biological Sciences Research Council (BBSRC) (BB/E023754/1, BB/G001596/1). We thank the BBSRC for a David Phillips Fellowship awarded to C.A.N. and the Royal Society for a University Research Fellowship awarded to T.A., R. Wilson for preparing libraries for sequencing, A. de Moura and I. Duggin for sharing unpublished data, and numerous colleagues for discussions.
Uncontrolled Keywords: general ,/dk/atira/pure/subjectarea/asjc/1000
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 07 Sep 2022 15:30
Last Modified: 21 Oct 2022 01:37
DOI: 10.1038/nature12650

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