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The bacterial cytolethal distending toxin (CDT) triggers a G2 cell cycle checkpoint in mammalian cells without preliminary induction of DNA strand breaks

Oncogene volume 18, pages 6296–6304 (1999)Cite this article

Abstract

The bacterial cytolethal distending toxin (CDT) was previously shown to arrest the tumor-derived HeLa cell line in the G2-phase of the cell cycle through inactivation of CDK1, a cyclin-dependent kinase whose state of activation determines entry into mitosis. We have analysed the effects induced in HeLa cells by CDT, in comparison to those induced by etoposide, a prototype anti-tumoral agent that triggers a G2 cell cycle checkpoint by inducing DNA damage. Both CDT and etoposide inhibit cell proliferation and induces the formation of enlarged mononucleated cells blocked in G2. In both cases, CDK1 from arrested cells could be re-activated both in vitro by dephosphorylation by recombinant Cdc25B phosphatase and in vivo by caffeine. However, the cell cycle arrest triggered by CDT, unlike etoposide, did not originate from DNA strand breaks as demonstrated in the single cell gel electrophoresis assay and by the absence of slowing down of S phase in synchronized cells. Together with additional observations on synchronized HeLa cells, our results suggest that CDT triggers a G2 cell cycle checkpoint that is initiated during DNA replication and that is independent of DNA damage.

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Acknowledgements

We are indebted to James Kaper for the gift of plasmid pDS 7.96. This work was supported in part by a grant from the European Community Program FAIR (number 1335). V Sert is recipient of a scholarship from Institut National de la Recherche Agronomique. This work was also supported by la Ligue Nationale contre le Cancer (to B Ducommun) and l'Association pour la Recherche contre le Cancer (B Ducommun).

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Authors and Affiliations

  1. Unité associée de Microbiologie Moléculaire, Institut National de la Recherche Agronomique et Ecole Nationale Vétérinaire, 23 chemin des capelles, Toulouse, 31076, Cedex, France

    V Sert, C Tasca, E Oswald & J De Rycke

  2. Unité Associée de Sécurité et Hygiène des Aliments, Institut National de la Recherche Agronomique et Ecole Vétérinaire, 23 chemin des capelles, Toulouse, 31076, Cedex, France

    L Bret-Bennis

  3. Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, 205 route de Narbonne, 31077, Toulouse, France

    C Cans & B Ducommun

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  1. V Sert
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Sert, V., Cans, C., Tasca, C. et al. The bacterial cytolethal distending toxin (CDT) triggers a G2 cell cycle checkpoint in mammalian cells without preliminary induction of DNA strand breaks. Oncogene 18, 6296–6304 (1999). https://doi.org/10.1038/sj.onc.1203007

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