A novel role for the Bcl-2 protein family: specific suppression of the RAD51 recombination pathway

Yannick Saintigny (1) , Anne Dumay (2) , Sarah Lambert (2) , Bernard Lopez (2)

1 LERA - Laboratoire d'Etudes de la Réparation de l'ADN
2 LMR - Laboratoire d'étude des Mécanismes de la recombinaison

The oncogenic role of Bcl-2 is generally attributed to its protective effect against apoptosis. Here, we show a novel role for Bcl-2: the speci®c inhibition of the conservative RAD51 recombination pathway. Bcl-2 or Bcl-X L overexpression inhibits UV-C-, gray or mutant p53-induced homologous recombination (HR). Moreover, Bcl-2 recombination inhibition is independent of the role of p53 in G 1 arrest. At an acute double-strand break in the recombination substrate, Bcl-2 speci®cally inhibits RAD51-dependent gene conversion without affecting non-conservative recombination. Bcl-2 consistently thwarts recombination stimulated by RAD51 overexpression and alters Rad51 protein by post-translation modi®cation. Moreover, a mutant G145A Bcl-2, which is defective in Bax interaction and in apoptosis repression, also inhibits recombination, showing that the death and recombination repression functions of Bcl-2 are separable. Inhibition of error-free repair pathways by Bcl-2 results in elevated frequencies of mutagenesis. The Bcl-2 gene therefore combines two separable cancer-prone phenotypes: apoptosis repression and a genetic instability/mutator phenotype. This dual phenotype could represent a mammalian version of the bacterial SOS repair system. Y.Saintigny and A.Dumay contributed equally to this work

Domaines: Cancer

Yannick Saintigny, Anne Dumay, Sarah Lambert, Bernard Lopez. A novel role for the Bcl-2 protein family: specific suppression of the RAD51 recombination pathway. EMBO Journal, 2001, 20 (10), pp.2596-2607. ⟨10.1093/emboj/20.10.2596⟩. ⟨cea-01938121⟩