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Polymerase d replicates both strands after homologous recombination-dependent fork restart
journal contribution
posted on 2023-06-09, 14:32 authored by Izumi Miyabe, Ken'ichi Mizuno, Andrea KeszthelyiAndrea Keszthelyi, Yasukazu Daigaku, Meliti Skouteri, Saed Mohebi, Thomas A Kunkel, Jo Murray, Antony CarrAntony CarrTo maintain genetic stability DNA must be replicated only once and replication completed even when individual replication forks are inactivated. Because fork inactivation is common, the passive convergence of an adjacent fork is insufficient to rescue all inactive forks. Thus, eukaryotic cells have evolved homologous recombination-dependent mechanisms to restart persistent inactive forks. Completing DNA synthesis via Homologous Recombination Restarted Replication (HoRReR) ensures cell survival, but at a cost. One such cost is increased mutagenesis caused by HoRReR being more error prone than canonical replication. This increased error rate implies that the HoRReR mechanism is distinct from that of a canonical fork. Here we exploit the fission yeast Schizosaccharomyces pombe to demonstrate that a DNA sequence duplicated by HoRReR during S phase is replicated semi-conservatively, but that both the leading and lagging strands are synthesised by DNA polymerase delta.
Funding
Single Molecule Imaging of the DNA Damage Response in Live Cells; G0250; EUROPEAN UNION; 268788
Which DNA polymerase functions during HR-dependent fork restart?; G0143; MRC-MEDICAL RESEARCH COUNCIL; G0801078
Replication fork stability and fork restart; G0745; MRC-MEDICAL RESEARCH COUNCIL; G1100074-E01/1
History
Publication status
- Published
File Version
- Accepted version
Journal
Nature Structural & Molecular BiologyISSN
1545-9993Publisher
Nature Publishing GroupExternal DOI
Issue
11Volume
22Page range
932-939Department 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
2018-08-15First Open Access (FOA) Date
2018-08-15First Compliant Deposit (FCD) Date
2018-08-15Usage metrics
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