title: Polymerase δ replicates both strands after homologous recombination-dependent fork restart.
abstract: To maintain genetic stability, DNA must be replicated only once per cell cycle, and replication must be completed even when individual replication forks are inactivated. Because fork inactivation is common, 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 because HoRReR is more error prone than canonical replication. This increased error rate implies the HoRReR mechanism is distinct from that of a canonical fork. Here we demonstrate, in Schizosaccharomyces pombe, that a DNA sequence duplicated by HoRReR during S phase is replicated semiconservatively, but both the leading and lagging strands are synthesized by DNA polymerase δ.
authors.affiliation: Genome Damage and Stability Centre, University of Sussex, Brighton, UK.
authors.forename: Izumi
authors.initials: I
authors.lastname: Miyabe
authors.affiliation: Genome Damage and Stability Centre, University of Sussex, Brighton, UK.
authors.forename: Ken'Ichi
authors.identifier: http://orcid.org/0000-0001-8115-7808
authors.initials: K
authors.lastname: Mizuno
authors.affiliation: Genome Damage and Stability Centre, University of Sussex, Brighton, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Keszthelyi
authors.affiliation: Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai, Japan.
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Daigaku
authors.affiliation: Genome Damage and Stability Centre, University of Sussex, Brighton, UK.
authors.forename: Meliti
authors.initials: M
authors.lastname: Skouteri
authors.affiliation: Genome Damage and Stability Centre, University of Sussex, Brighton, UK.
authors.forename: Saed
authors.initials: S
authors.lastname: Mohebi
authors.affiliation: Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Kunkel
authors.affiliation: Genome Damage and Stability Centre, University of Sussex, Brighton, UK.
authors.forename: Johanne M
authors.initials: JM
authors.lastname: Murray
authors.affiliation: Genome Damage and Stability Centre, University of Sussex, Brighton, UK.
authors.forename: Antony M
authors.initials: AM
authors.lastname: Carr
mesh_terms: D002455:Cell Division; D004258:DNA Polymerase III / Q000378:metabolism*; D004261:DNA Replication; D059765:Homologous Recombination; D012568:Schizosaccharomyces / Q000201:enzymology* / Q000235:genetics / Q000502:physiology
chemical_list: D004258:DNA Polymerase III