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Article Dans Une Revue Scientific Reports Année : 2016

Cell resistance to the cytolethal distending toxin involves an association of DNA repair mechanisms

Elisabeth Bezine
  • Fonction : Auteur
Yann Malaisé
  • Fonction : Auteur
  • PersonId : 1018734
Aurore Loeuillet
  • Fonction : Auteur
Marianne Chevalier
  • Fonction : Auteur
Bernard Salles
  • Fonction : Auteur
  • PersonId : 1204694

Résumé

The Cytolethal Distending Toxin (CDT), produced by many bacteria, has been associated with various diseases including cancer. CDT induces DNA double-strand breaks (DSBs), leading to cell death or mutagenesis if misrepaired. At low doses of CDT, other DNA lesions precede replication-dependent DSB formation, implying that non-DSB repair mechanisms may contribute to CDT cell resistance. To address this question, we developed a proliferation assay using human cell lines specifically depleted in each of the main DNA repair pathways. Here, we validate the involvement of the two major DSB repair mechanisms, Homologous Recombination and Non Homologous End Joining, in the management of CDT-induced lesions. We show that impairment of single-strand break repair (SSBR), but not nucleotide excision repair, sensitizes cells to CDT, and we explore the interplay of SSBR with the DSB repair mechanisms. Finally, we document the role of the replicative stress response and demonstrate the involvement of the Fanconi Anemia repair pathway in response to CDT. In conclusion, our work indicates that cellular survival to CDT-induced DNA damage involves different repair pathways, in particular SSBR. This reinforces a model where CDT-related genotoxicity primarily involves SSBs rather than DSBs, underlining the importance of cell proliferation during CDT intoxication and pathogenicity.
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hal-01602345 , version 1 (28-05-2020)

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Elisabeth Bezine, Yann Malaisé, Aurore Loeuillet, Marianne Chevalier, Elisa Boutet-Robinet, et al.. Cell resistance to the cytolethal distending toxin involves an association of DNA repair mechanisms. Scientific Reports, 2016, 6, pp.1-15. ⟨10.1038/srep36022⟩. ⟨hal-01602345⟩
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