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Genes 2016, 7(12), 134;

The Causes and Consequences of Topological Stress during DNA Replication

Genome Damage and Stability Centre, Science Park Road, University of Sussex, Falmer, Brighton, East Sussex BN1 9RQ, UK
These authors contributed equally to this manuscript.
Author to whom correspondence should be addressed.
Academic Editor: Eishi Noguchi
Received: 31 October 2016 / Revised: 11 December 2016 / Accepted: 14 December 2016 / Published: 21 December 2016
(This article belongs to the Special Issue DNA Replication Controls)
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The faithful replication of sister chromatids is essential for genomic integrity in every cell division. The replication machinery must overcome numerous difficulties in every round of replication, including DNA topological stress. Topological stress arises due to the double-stranded helical nature of DNA. When the strands are pulled apart for replication to occur, the intertwining of the double helix must also be resolved or topological stress will arise. This intrinsic problem is exacerbated by specific chromosomal contexts encountered during DNA replication. The convergence of two replicons during termination, the presence of stable protein-DNA complexes and active transcription can all lead to topological stresses being imposed upon DNA replication. Here we describe how replication forks respond to topological stress by replication fork rotation and fork reversal. We also discuss the genomic contexts where topological stress is likely to occur in eukaryotes, focusing on the contribution of transcription. Finally, we describe how topological stress, and the ways forks respond to it, may contribute to genomic instability in cells. View Full-Text
Keywords: DNA replication; DNA topology; DNA topoisomerases; transcription; fork rotation; fork reversal DNA replication; DNA topology; DNA topoisomerases; transcription; fork rotation; fork reversal

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Keszthelyi, A.; Minchell, N.E.; Baxter, J. The Causes and Consequences of Topological Stress during DNA Replication. Genes 2016, 7, 134.

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