Nitric oxide upregulates expression of DNA-PKcs to protect cells from DNA-damaging anti-tumour agents

Nitric-oxide synthase (NOS) activity has been detected in many human tumour s, although its function is unclear. Here we show that exposure of cells to nitric oxide (NO) results in a 4-5-fold increase in expression of the DNA- dependent protein-kinase catalytic subunit (DNA-PKcs), one of the key enzym es involved in repairing double-stranded DNA breaks. This NO-mediated incre ase in enzymatically active DNA-PK not only protects cells from the toxic e ffects of NO, but also provides crossprotection against clinically importan t DNA-damaging agents, such as X-ray radiation, adriamycin, bleomycin and c isplatin. The NO-mediated increase in DNA-PKcs described here demonstrates the presence of a new and highly effective NO-mediated mechanism for DNA re pair.