Abstract
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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis / genetics*
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Cell Cycle Proteins / analysis
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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Cell Nucleus / chemistry
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Cell Survival / genetics
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Flow Cytometry
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Humans
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Indicators and Reagents
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Mammals
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Molecular Sequence Data
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Plasmids
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Propidium
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Proto-Oncogene Proteins c-bcl-2 / analysis
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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RNA, Antisense / pharmacology
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Schizosaccharomyces / cytology*
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Schizosaccharomyces / genetics*
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Schizosaccharomyces / metabolism
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Sequence Homology, Amino Acid
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Signal Transduction / physiology
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Transfection
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Two-Hybrid System Techniques
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bcl-X Protein
Substances
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BCL2L1 protein, human
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Cell Cycle Proteins
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Indicators and Reagents
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Proto-Oncogene Proteins c-bcl-2
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RNA, Antisense
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bcl-X Protein
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rad9 protein
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Propidium