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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 mu g 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.
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Submitted on : Friday, May 29, 2020 - 8:25:12 AM
Last modification on : Tuesday, October 19, 2021 - 2:24:25 PM

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Yoann Fedor, Julien Vignard, Marie-Laure Travers, Elisa Boutet-Robinet, Claude Watrin, et al.. From single-strand breaks to double-strand breaks during S-phase: a new mode of action of the Escherichia coli Cytolethal Distending Toxin. Cellular Microbiology, Wiley, 2013, 15 (1), pp.1 - 15. ⟨10.1111/cmi.12028⟩. ⟨hal-02647902⟩

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