Bax and Bid, two proapoptotic Bcl-2 family members, inhibit homologous recombination, independently of apoptosis regulation.
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.
Dumay
A
A
UMR 217 CNRS/CEA, DSV, DRR, Fontenay aux Roses Cédex, France.
Laulier
C
C
Bertrand
P
P
Saintigny
Y
Y
Lebrun
F
F
Vayssière
J-L
JL
Lopez
B S
BS
D000818:Animals; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism*; D015153:Blotting, Western; D016466:CHO Cells / Q000378:metabolism / Q000528:radiation effects; D006224:Cricetinae; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D005455:Fluorescent Antibody Technique; D005720:Gamma Rays; D006801:Humans; D051135:Rad51 Recombinase / Q000378:metabolism; D011995:Recombination, Genetic; D029701:Saccharomyces cerevisiae Proteins; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism*
D051023:BH3 Interacting Domain Death Agonist Protein; D029701:Saccharomyces cerevisiae Proteins; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D051135:Rad51 Recombinase; C037725:SCEI protein, S cerevisiae; D015252:Deoxyribonucleases, Type II Site-Specific