The p53 tumor-suppressor gene integrates numerous signals that control cell life and death. Several novel molecules involved in p53 signaling, including Chk2 , p53R2, p53AIP1, Noxa, PIDD, and PID/MTA2, were recently discovered. The checkpoint kinase Chk2 is the mammalian homologue of yeast Cds1/Rad53. In response to DNA damage, the checkpoint kinase ATM phosphorylates and activates Chk2, which in turn directly phosphorylates and activates p53. Chk2 serves as ATM downstream effector to mediate activation of p53. Chk2 also phosphorylates and activates BRCA1, the product of a tumor suppressor gene that is mutated in breast and ovarian cancer.