Programmed cell death 6, a novel p53‐responsive gene, targets to the nucleus in the apoptotic response to DNA damage

The cellular response to genotoxic stress is multifaceted in nature. Following DNA damage, the tumor suppressor gene p53 activates and plays critical roles in cell cycle arrest, activation of DNA repair and in the event of irreparable damage, induction of apoptosis. The breakdown of apoptosis causes the accumulation of mutant cells. The elucidation of the mechanism for the p53‐dependent apoptosis will be crucial in applying the strategy for cancer patients. However, the mechanism of p53‐dependent apoptosis remains largely unclear. Here, we carried out C h IP followed by massively parallel DNA sequencing assay ( C h IP ‐seq) to uncover mechanisms of apoptosis. Using C h IP ‐seq, we identified PDCD 6 as a novel p53‐responsive gene. We determined putative p53‐binding sites that are important for p53 regulation in response to DNA damage in the promoter region of PDCD 6. Knockdown of PDCD 6 suppressed p53‐dependent apoptosis. We also observed that cytochrome c release and the cleavage of PARP by caspase‐3 were suppressed by depletion of PDCD 6. We further observed that PDCD 6 localizes in the nucleus in response to DNA damage. We identified the nuclear localization signal of PDCD 6 and, importantly, the nuclear accumulation of PDCD 6 significantly induced apoptosis after genotoxic stress. Therefore, we conclude that a novel p53‐responsive gene PDCD 6 is accumulated in the nucleus and induces apoptosis in response to DNA damage.