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

Oncogene volume 25, pages 3196–3205 (2006)Cite this article

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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  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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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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