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

Oncogene. 2006 May 25;25(22):3196-205. doi: 10.1038/sj.onc.1209344.

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 gamma-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • BH3 Interacting Domain Death Agonist Protein / metabolism*
  • Blotting, Western
  • CHO Cells / metabolism
  • CHO Cells / radiation effects
  • Cricetinae
  • Deoxyribonucleases, Type II Site-Specific / metabolism
  • Fibroblasts / metabolism
  • Fibroblasts / radiation effects
  • Fluorescent Antibody Technique
  • Gamma Rays
  • Humans
  • Rad51 Recombinase / metabolism
  • Recombination, Genetic*
  • Saccharomyces cerevisiae Proteins
  • Ultraviolet Rays
  • bcl-2-Associated X Protein / metabolism*
  • bcl-X Protein / metabolism*

Substances

  • BH3 Interacting Domain Death Agonist Protein
  • Saccharomyces cerevisiae Proteins
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • Rad51 Recombinase
  • SCEI protein, S cerevisiae
  • Deoxyribonucleases, Type II Site-Specific