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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

Y. Fedor, J. Vignard, M-L Nicolau-Travers, E. Boutet-Robinet, C. Watrin, B. Salles, G. Mirey
Published 2013 · Biology, Medicine

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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.
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