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

Deegan, Tom D, Baxter, Jonathan, Ortiz Bazán, María Ángeles, Yeeles, Joseph T P and Labib, Karim P M (2019) Pif1-Family helicases support fork convergence during DNA replication termination in eukaryotes. Molecular Cell, 74 (2). 231-244.e9. ISSN 1097-4164

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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.

Item Type: Article
Keywords: DNA replication
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Research Centres and Groups: Genome Damage and Stability Centre
Subjects: Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics > QH0447 Genes. Alleles. Genome
Depositing User: Jon Baxter
Date Deposited: 25 Jun 2019 08:50
Last Modified: 08 Oct 2019 07:01
URI: http://sro.sussex.ac.uk/id/eprint/84526

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Project NameSussex Project NumberFunderFunder Ref
Investigating how replication fork rotation causes chromosomal instability during S phaseG1903BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCILBB/N007344/1