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The causes and consequences of topological stress during DNA replication

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journal contribution
posted on 2023-06-09, 08:52 authored by Andrea KeszthelyiAndrea Keszthelyi, Nicola Minchell, Jon BaxterJon Baxter
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

Funding

Regulating replication fork rotation to maintain genome stability - URF 3 year extension; G1704; ROYAL SOCIETY; UF140706

Investigating how replication fork rotation causes chromosomal instability during S phase; G1903; BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCIL; BB/N007344/1

History

Publication status

  • Published

File Version

  • Published version

Journal

Genes

ISSN

2073-4425

Publisher

MDPI

Issue

12

Volume

7

Page range

134

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Research groups affiliated with

  • Genome Damage and Stability Centre Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2017-11-15

First Open Access (FOA) Date

2017-11-15

First Compliant Deposit (FCD) Date

2017-11-15

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