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

Izumi Miyabe, Ken'Ichi Mizuno, Andrea Keszthelyi, Yasukazu Daigaku, Meliti Skouteri, Saed Mohebi, Thomas A. Kunkel, Johanne M. Murray, Antony M. Carr

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)932-938
Number of pages7
JournalNature Structural and Molecular Biology
Volume22
Issue number11
DOIs
Publication statusPublished - 2015 Nov 4

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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