title: From single-strand breaks to double-strand breaks during S-phase: a new mode of action of the Escherichia coli Cytolethal Distending Toxin.
abstract: The Cytolethal Distending Toxin (CDT) is a genotoxin produced by several pathogenic bacteria. It is generally admitted that CDT induces double-strand breaks (DSB) and cell cycle arrest in G2/M-phase, in an ATM-dependent manner. Most of these results were obtained at high dose (over 1 μg ml(-1) ) of CDT and late after treatment (8-24 h). We provide here evidence that the Escherichia coli CDT (EcCDT) - at low dose (50 pg ml(-1)  or LD50) and early after treatment (3-6 h) - progressively induces DNA DSB, mostly in S-phase. DSB formation is related to the single-strand breaks induction by CDT, converted into DSB during the S-phase. We also show that homologous recombination is mobilized to these S-phase-associated DSB. This model unveils a new mechanism for CDT genotoxicity that may play a role in cells partly deficient in homologous recombination.
authors.affiliation: INRA, UMR1331, Toxalim, Research Centre in Food Toxicology, F-31027, Toulouse, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Fedor
authors.forename: J
authors.initials: J
authors.lastname: Vignard
authors.forename: M-L
authors.initials: ML
authors.lastname: Nicolau-Travers
authors.forename: E
authors.initials: E
authors.lastname: Boutet-Robinet
authors.forename: C
authors.initials: C
authors.lastname: Watrin
authors.forename: B
authors.initials: B
authors.lastname: Salles
authors.forename: G
authors.initials: G
authors.lastname: Mirey
mesh_terms: D001427:Bacterial Toxins / Q000633:toxicity*; D002875:Chromosomes / Q000187:drug effects*; D053903:DNA Breaks, Double-Stranded; D053904:DNA Breaks, Single-Stranded; D004847:Epithelial Cells / Q000166:cytology / Q000382:microbiology*; D004926:Escherichia coli / Q000472:pathogenicity*; D006367:HeLa Cells; D059765:Homologous Recombination; D006801:Humans; D016196:S Phase
chemical_list: D001427:Bacterial Toxins; C067044:cytolethal distending toxin