When cells encounter genotoxic stress, sensors for DNA lesions stabilize and 
activate p53; the signals involved, however, are largely unclear. Inorganic 
arsenite is a ubiquitous environmental contaminant associated with an increased 
risk of lung and skin damage and cancer. Although DNA double-strand breaks and 
apoptosis may relate to arsenite-induced damage and carcinogenesis, the 
mechanism of action remains obscure. Here, we find that, in human embryo lung 
fibroblast (HELF) cells, arsenite induces the activation of dependent protein 
kinase catalytic subunit (DNA-PKcs), which then phosphorylates and activates 
c-Jun N-terminal kinases 2 (JNK2), but not JNK1. As a positive regulator of p53, 
JNK2 binds to p53 and prevents p53 from murine double minute 2 (mdm2)-mediated, 
ubiquitin-proteasome-dependent degradation. Knockdown of DNA-PKcs/JNK2 signal 
pathway or p53 reduces apoptosis but elevates the DNA damage induced by a high 
level of arsenite. These results suggest that DNA-PKcs-mediated stabilization of 
p53 by JNK2 is involved in arsenite-induced DNA damage and apoptosis.