The causes and consequences of topological stress during DNA replication

Keszthelyi, Andrea, Minchell, Nicola and Baxter, Jon (2016) The causes and consequences of topological stress during DNA replication. Genes, 7 (12). p. 134. ISSN 2073-4425

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Abstract

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

Item Type: Article
Keywords: DNA replication DNA topology genomic instability
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Research Centres and Groups: Genome Damage and Stability Centre
Subjects: Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics
Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics > QH0447 Genes. Alleles. Genome
Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics > QH0460 Mutations
Depositing User: Jon Baxter
Date Deposited: 15 Nov 2017 15:27
Last Modified: 15 Nov 2017 15:28
URI: http://sro.sussex.ac.uk/id/eprint/71282

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Project NameSussex Project NumberFunderFunder Ref
Investigating how replication fork rotation causes chromosomal instability during S phaseG1903BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCILBB/N007344/1
Regulating replication fork rotation to maintain genome stability - URF 3 year extensionG1704ROYAL SOCIETYUF140706