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Poster De Conférence Année : 2015

Overview of the DNA repair pathways involved in response to the cytolethal distending toxin

Elisabeth Bezine
  • Fonction : Auteur
Julien Vignard
Marianne Chevalier
  • Fonction : Auteur
Bernard Salles
  • Fonction : Auteur
Gladys Mirey

Résumé

The Cytolethal Distending Toxin (CDT) is produced by many pathogenic gram-negative bacteria and its production has been associated to various diseases, including tumorigenesis. The CDT-related pathogenicity relies on the action of the catalytic subunit CdtB, which has been shown to induce double-strand breaks (DSB) on the host cell DNA. Different studies pointed out the importance of DSB repair mechanisms for cells to survive CDT, emphasizing on the homologous recombination repair pathway. Previously, we reported that another type of DNA lesion precede DSB formation through replicative stress. Since various repair pathways allow cells to respond different type of DNA damage, we speculated that non-DSB repair mechanisms might contribute to the cellular resistance to CDT-mediated genotoxicity. To address this question, we use an innovative proliferation assay, on human cell lines depleted in the major DNA repair pathways. Firstly, we confirm that homologous recombination is involved in the management of CDT-induced lesions, but also of Non Homologous End Joining, the second major DSB repair mechanism. Next, we show that nucleotide excision repair is not important to take care of CDT-induced damage, whereas base excision repair (BER) impairment sensitize CDT-treated cells, suggesting that CDT induce single-strand breaks or base modifications. Finally, we demonstrate for the first time the involvement and the activation of the Fanconi Anemia repair pathway in response to CDT. In conclusion, our work supports that CDT-induced damage are plurals and involve different repair pathways. This reinforces a model where CDT induces base damage and underlines the importance of cell proliferation to generate DNA double-strand break damage.
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Dates et versions

hal-02740247 , version 1 (02-06-2020)

Identifiants

  • HAL Id : hal-02740247 , version 1
  • PRODINRA : 343106

Citer

Elisabeth Bezine, Julien Vignard, Marianne Chevalier, Elisa Boutet-Robinet, Bernard Salles, et al.. Overview of the DNA repair pathways involved in response to the cytolethal distending toxin. The 6th EMBO Meeting, Sep 2015, Birmingham, United Kingdom. 2015. ⟨hal-02740247⟩
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