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Polymerase d replicates both strands after homologous recombination-dependent fork restart

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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 Carr
To 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 Biology

ISSN

1545-9993

Publisher

Nature Publishing Group

Issue

11

Volume

22

Page range

932-939

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

2018-08-15

First Open Access (FOA) Date

2018-08-15

First Compliant Deposit (FCD) Date

2018-08-15

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