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Nature Cell Biology 4, 865–870 (1 November 2002) | doi:10.1038/ncb869

PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2

Shutong Yang , Christin Kuo , John E. Bisi & Myung K. Kim

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 γ irradiation-induced apoptosis. The DNA damage checkpoint kinase hCds1/Chk2 is necessary for p53-dependent apoptosis after γ irradiation. In addition, γ irradiation-induced apoptosis also occurs through p53-independent mechanisms, although the molecular mechanism remains largely unknown. Here, we report that hCds1/Chk2 mediates γ 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 γ irradiation-induced apoptosis.