title: Replication fork reversal in eukaryotes: from dead end to dynamic response.
abstract: The remodelling of replication forks into four-way junctions following replication perturbation, known as fork reversal, was hypothesized to promote DNA damage tolerance and repair during replication. Albeit conceptually attractive, for a long time fork reversal in vivo was found only in prokaryotes and specific yeast mutants, calling its evolutionary conservation and physiological relevance into question. Based on the recent visualization of replication forks in metazoans, fork reversal has emerged as a global, reversible and regulated process, with intriguing implications for replication completion, chromosome integrity and the DNA damage response. The study of the putative in vivo roles of recently identified eukaryotic factors in fork remodelling promises to shed new light on mechanisms of genome maintenance and to provide novel attractive targets for cancer therapy.
authors.affiliation: 1] Institute of Molecular Cancer Research, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. [2] The Novo Nordisk Foundation Center for Protein Research, 2200 Copenhagen, Denmark.
authors.forename: Kai J
authors.initials: KJ
authors.lastname: Neelsen
authors.affiliation: Institute of Molecular Cancer Research, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Massimo
authors.initials: M
authors.lastname: Lopes
mesh_terms: D000818:Animals; D002843:Chromatin / Q000502:physiology; D004249:DNA Damage / Q000502:physiology; D004261:DNA Replication / Q000502:physiology; D006801:Humans
chemical_list: D002843:Chromatin