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

Miyabe, Izumi, Mizuno, Ken'ichi, Keszthelyi, Andrea, Daigaku, Yasukazu, Skouteri, Meliti, Mohebi, Saed, Kunkel, Thomas A, Murray, Johanne and Carr, Antony M (2015) Polymerase δ replicates both strands after homologous recombination-dependent fork restart. Nature Structural & Molecular Biology, 22 (11). pp. 932-939. ISSN 1545-9993

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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.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Research Centres and Groups: Genome Damage and Stability Centre
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Depositing User: Paula Amiet-West
Date Deposited: 15 Aug 2018 07:52
Last Modified: 15 Aug 2018 07:55
URI: http://srodev.sussex.ac.uk/id/eprint/77835

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