For many years, p53 was viewed as the cell's principal regulator of apoptosis. Its function appeared relatively straightforward. DNA damage activated p53, p53 stopped the cell cycle while repair occurred, and if the damage proved too severe, p53 activated genes such as BAX, PUMA, and NOXA that caused the mitochondria to release cytochrome c and initiate apoptotic cell death. This picture established p53 as the "guardian of the genome," but it also suggested that its decision-