The promyelocytic leukaemia (PML) gene is translocated in most acute promyelocytic leukaemias and encodes a tumour suppressor protein. PML is involved in multiple apoptotic pathways and is thought to be pivotal in irradiation-induced apoptosis. The DNA damage checkpoint kinase hCds1/Chk2 is necessary for p53-dependent apoptosis after irradiation. In addition, irradiation-induced apoptosis also occurs through p53-independent mechanisms, although the molecular mechanism remains largely unknown. Here, we report that hCds1/Chk2 mediates irradiation-induced apoptosis in a p53-independent manner through an ataxia telangiectasia-mutated (ATM)−hCds1/Chk2−PML pathway. Our results provide the first evidence of a functional relationship between PML and a checkpoint kinase in irradiation-induced apoptosis.
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irradiation-induced apoptosis. The DNA damage checkpoint kinase hCds1/Chk2 is necessary for p53-dependent apoptosis after 
