Nature Cell Biology
2, 339 - 345 (2000)
Published online: 10 May 2000; | doi:10.1038/35014028
Nitric oxide upregulates expression of DNA-PKcs to protect cells from DNA-damaging anti-tumour agentsWeiming Xu1, Lizhi Liu1, Graeme C. M. Smith2, 3
& lan G. Charles11
The Wolfson Institute for Biomedical Research, The Cruciform Building, University College London, Gower Street, London WC1E 6BT, UK
2
Wellcome Trust/CRC Institute and Department of Zoology, Cambridge University,
Tennis Court Road, Cambridge CB2 1QR, UK
3
Present address: KuDOS Pharmaceuticals Ltd. Cambridge, CB4 4WG, UK
Correspondence should be addressed to lan G. Charles rmgzigc@ucl.ac.ukNitric-oxide synthase (NOS) activity has been detected in many human tumours, 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 enzymes involved in repairing double-stranded DNA breaks. This NO-mediated increase in enzymatically active DNA-PK not only protects cells from the toxic effects of NO, but also provides crossprotection against clinically important DNA-damaging agents, such as X-ray radiation, adriamycin, bleomycin and cisplatin. The NO-mediated increase in DNA-PKcs described here demonstrates the presence of a new and highly effective NO-mediated mechanism for DNA repair.
|
