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Bax and Bid, two proapoptotic Bcl-2 family members, inhibit homologous recombination, independently of apoptosis regulation

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Abstract

In order to analyse the relationships between regulation of apoptosis and homologous recombination (HR), we overexpressed proapoptotic Bax or only-BH3 Bid proteins or antiapoptotic Bcl-2 or Bcl-XL, in hamster CHO cells or in SV40-transformed human fibroblasts. We measured HR induced by γ-rays, UVC or a specific double-strand cleavage targeted in the recombination substrate by the meganuclease I-SceI. We show here that the induction of both recombinant cells and recombinant colonies was impaired when expressing Bcl-2 family members, in hamster as well as in human cells. Moreover, the pro- as well as antiapoptotic Bcl-2 family members inhibited HR, independently of degradation of the RAD51 recombination protein and of their impact on apoptosis. These data reveal a mechanism of HR downregulation by potentially proapoptotic proteins, distinct from and parallel to degradation of recombination proteins, a situation that should also optimize the efficiency of programmed cell death.

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Acknowledgements

We thank Drs J Adams and S Cory for providing us the Y28ABcl-2 expression vector, Dr SJ Korsmeyer for the G145ABcl-2 mutant expression, Dr S Desagher for the Bid expression vector, Dr E May for the Bax expression vector, Dr M Jasin for the DRA10 cell line and the pDR-GFP plasmid, Dr R Monat for GM639 cell line and Dr D Marsh for critical reading of the manuscript. AD was supported by a fellowship from INSTN/EDF and then by Ministère de l’Education Nationale; CL is supported by a fellowship from INSTN. This work was supported by La Ligue Nationale contre le Cancer ‘Equipe labéllisée, La Ligue 2005’.

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Authors and Affiliations

  1. UMR 217 CNRS/CEA, DSV, DRR, Fontenay aux RosesCédex, France

    A Dumay, C Laulier, P Bertrand, Y Saintigny, F Lebrun & B S Lopez

  2. CNRS-FRE 2445, Laboratoire de génétique et de biologie cellulaire, Université Versailles/Saint Quentin-en-Yvelines, Versailles Cédex, France

    A Dumay & J-L Vayssière

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  1. A Dumay
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  2. C Laulier
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  3. P Bertrand
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  4. Y Saintigny
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  5. F Lebrun
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  7. B S Lopez
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Correspondence to B S Lopez.

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Dumay, A., Laulier, C., Bertrand, P. et al. Bax and Bid, two proapoptotic Bcl-2 family members, inhibit homologous recombination, independently of apoptosis regulation. Oncogene 25, 3196–3205 (2006). https://doi.org/10.1038/sj.onc.1209344

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