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-xL, 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-xL. 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.
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Acknowledgements
We thank J. C. Reed and R. Jove for comments on the manuscript; S. Dalton for technical assistance; and the Molecular Biology, Flow Cytometry, and Molecular Imaging core facilities of Moffitt Cancer Center. This work was partially supported by grants from the ACS (IRG032) and NIH (CA82197-01) to H.-G.W., and grants from the NIH (GM52493 and CA68446) and DOE (DE-FG07-96ER62309) to H.B.L.
Correspondence and requests for materials should be addressed to H.-G.W.
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Komatsu, K., Miyashita, T., Hang, H. et al. Human homologue of S. pombe Rad9 interacts with BCL-2/BCL-xL and promotes apoptosis. Nat Cell Biol 2, 1–6 (2000). https://doi.org/10.1038/71316
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DOI: https://doi.org/10.1038/71316
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