Pif1-family helicases support fork convergence during DNA replication termination in eukaryotes

Thomas Deegan (Lead / Corresponding author), Jonathan Baxter, Maria Ortiz Bazan, Joseph T. P. Yeeles, Karim Labib (Lead / Corresponding author)

Research output: Contribution to journalArticle

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Abstract

The convergence of two DNA replication forks creates unique problems during DNA replication termination. In E. coli and SV40, the release of torsional strain by type II topoisomerases is critical for converging replisomes to complete DNA synthesis, but the pathways that mediate fork convergence in eukaryotes are unknown. We studied the convergence of reconstituted yeast replication forks that include all core replisome components and both type I and type II topoisomerases. We found that most converging forks stall at a very late stage, indicating a role for additional factors. We showed that the Pif1 and Rrm3 DNA helicases promote efficient fork convergence and completion of DNA synthesis, even in the absence of type II topoisomerase. Furthermore, Rrm3 and Pif1 are also important for termination of plasmid DNA replication in vivo. These findings identify a eukaryotic pathway for DNA replication termination that is distinct from previously characterized prokaryotic mechanisms.

Original languageEnglish
Pages (from-to)231-244.e9
Number of pages24
JournalMolecular Cell
Volume74
Issue number2
Early online date5 Mar 2019
DOIs
Publication statusPublished - 18 Apr 2019

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Keywords

  • CMG helicase
  • DNA replication termination
  • Pif1
  • Rrm3
  • Top2
  • chromosome replication
  • fork convergence
  • replisome
  • topoisomerase

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