Human homologue of S. pombe Rad9 interacts with BCL-2/BCL-xL and promotes apoptosis

Nat Cell Biol. 2000 Jan;2(1):1-6. doi: 10.1038/71316.


DNA damage induces apoptosis through a signalling pathway that can be suppressed by the BCL-2 protein, but the mechanism by which DNA damage does this is unknown. Here, using yeast two-hybrid and co-immunoprecipitation studies, we show that RAD9, a human protein involved in the control of a cell-cycle checkpoint, interacts with the anti-apoptotic Bcl-2-family proteins BCL-2 and BCL-x L, but not with the pro-apoptotic BAX and BAD. When overexpressed in mammalian cells, RAD9 induces apoptosis that can be blocked by BCL-2 or BCL-x L. Conversely, antisense RAD9 RNA suppresses cell death induced by methyl methanesulphonate. These findings indicate that RAD9 may have a new role in regulating apoptosis after DNA damage, in addition to its previously described checkpoint-control and other radioresistance-promoting functions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Cell Cycle Proteins / analysis
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Nucleus / chemistry
  • Cell Survival / genetics
  • Flow Cytometry
  • Humans
  • Indicators and Reagents
  • Mammals
  • Molecular Sequence Data
  • Plasmids
  • Propidium
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Antisense / pharmacology
  • Schizosaccharomyces / cytology*
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction / physiology
  • Transfection
  • Two-Hybrid System Techniques
  • bcl-X Protein


  • BCL2L1 protein, human
  • Cell Cycle Proteins
  • Indicators and Reagents
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Antisense
  • bcl-X Protein
  • rad9 protein
  • Propidium