Avoiding chromosome pathology when replication forks collide

Rudolph, Christian J., Upton, Amy L., Stockum, Anna, Nieduszynski, Conrad A. ORCID: https://orcid.org/0000-0003-2001-076X and Lloyd, Robert G. (2013) Avoiding chromosome pathology when replication forks collide. Nature, 500 (7464). pp. 608-611. ISSN 0028-0836

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Chromosome duplication normally initiates through the assembly of replication fork complexes at defined origins. DNA synthesis by any one fork is thought to cease when it meets another travelling in the opposite direction, at which stage the replication machinery may simply dissociate before the nascent strands are finally ligated. But what actually happens is not clear. Here we present evidence consistent with the idea that every fork collision has the potential to threaten genomic integrity. In Escherichia coli this threat is kept at bay by RecG DNA translocase and by single-strand DNA exonucleases. Without RecG, replication initiates where forks meet through a replisome assembly mechanism normally associated with fork repair, replication restart and recombination, establishing new forks with the potential to sustain cell growth and division without an active origin. This potential is realized when roadblocks to fork progression are reduced or eliminated. It relies on the chromosome being circular, reinforcing the idea that replication initiation is triggered repeatedly by fork collision. The results reported raise the question of whether replication fork collisions have pathogenic potential for organisms that exploit several origins to replicate each chromosome.

Item Type: Article
Additional Information: Funding Information: Acknowledgements We thankT. HoriuchiandD.Sherrattfor E. coli strains,A. Mahdi for help with DNA extractions, S. Malla and M. Blythe for deep sequencing, S. Demolli and D. Ivanova for control experiments, and C. Buckman and L. Harris for assistance. This work was supported by grants from the MRC (R.G.L., G0800970), the Leverhulme Trust (C.J.R.) and the BBSRC (C.A.N., BB/E023754/1).
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: 08 Sep 2022 07:31
Last Modified: 21 Oct 2022 01:37
URI: https://ueaeprints.uea.ac.uk/id/eprint/87882
DOI: 10.1038/nature12312

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