title: The Causes and Consequences of Topological Stress during DNA Replication.
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.
authors.affiliation: Genome Damage and Stability Centre, Science Park Road, University of Sussex, Falmer, Brighton, East Sussex BN1 9RQ, UK. A.Keszthelyi@sussex.ac.uk.
authors.forename: Andrea
authors.initials: A
authors.lastname: Keszthelyi
authors.affiliation: Genome Damage and Stability Centre, Science Park Road, University of Sussex, Falmer, Brighton, East Sussex BN1 9RQ, UK. N.Minchell@sussex.ac.uk.
authors.forename: Nicola E
authors.initials: NE
authors.lastname: Minchell
authors.affiliation: Genome Damage and Stability Centre, Science Park Road, University of Sussex, Falmer, Brighton, East Sussex BN1 9RQ, UK. Jon.Baxter@sussex.ac.uk.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Baxter
keywords: DNA replication; DNA topoisomerases; DNA topology; fork reversal; fork rotation; transcription