Human homologue of S-pombe Rad9 interacts with BCL-2/BCL-x(L) and promotes apoptosis

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 RADS, a human protein involved in the control of a cell-cycle checkpoint, interacts with the anti-apoptotic Bel-2-family proteins BCL-2 and BCL-x(L), but not with the pro-apoptotic BAX and BAD. When overexpressed in mammalian cells, RADS induces apoptosis that can be blocked by BCL-2 or BCL-x(L), Conversely, antisense RADS RNA suppresses cell death induced by methyl methanesulphonate, These findings indicate that RADS may have a new role in regulating apoptosis after DNA damage, in addition to its previously described checkpoint-control and other radioresistance-promoting functions.