Decreased DNA-PK activity in human cancer cells exhibiting hypersensitivity to low-dose irradiation

Article metrics


Low-dose hyper-radiosensitivity (HRS) (below 0.5 Gy) has been extensively documented in the past few years. The molecular basis of this phenomenon remains largely unknown and the purpose of this study was to investigate the possible implication of the DNA repair DNA-PK complex. The activity of the DNA-PK complex, i.e. Ku DNA-end binding activity and kinase activity of the whole complex, was studied in 10 human cancer cell lines, 2 h after 0.2, 0.5 and 1 Gy irradiation. After low-dose irradiation (0.2 Gy), a marked decrease in DNA-PK activity was found in all six cell lines exhibiting HRS, whereas the DNA-PK activity was increased in the four cell lines which did not exhibit HRS. This modulation of DNA-PK activity was a rapid phenomenon occurring within the 2 h following low-dose radiation exposure. These data strongly suggest the implication of the DNA-PK repair complex in the HRS phenomenon. © 2000 Cancer Research Campaign

Change history

  • 16 November 2011

    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication


  1. Allalunis-Turner MJ, Zia PKY, Barron GM, Mirzayans R and Day, III RS (1995) Radiation-induced DNA damage repair in cells of a radiosensitive human malignant glioma cell line. Radiat Res 144: 288–293

  2. Badie C, Iliakis G and Foray N (1995) Induction and rejoining of DNA double-strand breaks and interphase chromosome breaks after exposure to X-rays in one normal and two hypersensitive human fibroblast cell lines. Radiat Res 144: 26–35

  3. Chan DW and Lees-Miller SP (1996) The DNA-dependent protein kinase is inactivated by autophosphorylation of the catalytic subunit. J Biol Chem 89: 36–41

  4. Finnie NJ, Gottlieb TM, Blunt T, Jeggo PA and Jackson SP (1995) DNA-dependent protein kinase activity is absent in xrs-6 cells: implications for site-specific recombination and DNA double-stand break repair. Proc Natl Acad Sci USA 92: 320–324

  5. Foray N, Priestley A, Alsbeih G, Badie C, Capulas EP, Arlett CF and Malaise EP (1997) Hypersensitivity of ataxia telangiectasia fibroblasts to ionizing radiation is associated with a repair deficiency of DNA double-strand breaks. Int J Radiat Biol 72: 271–283

  6. Gottlieb TM and Jackson SP (1993) The DNA-dependent protein kinase requirement for DNA ends and association with Ku antigen. Cell 72: 131–142

  7. Jeggo PA (1998) Identification of genes involved in repair of DNA double strand breaks in mammalian cells. Radiat Res 150: S80–91

  8. Joiner MC, Lambin P, Malaise EP, Robson T, Arrand JE, Skov KA and Marples B (1996) Hypersensitivity to very-low single radiation doses: its relationship to adaptative response and induced radioresistance. Mutat Res 358: 171–183

  9. Jongmans W, Artuso M, Vuillaume M, Bresil H, Jackson SP and Hall J (1996) The role of Ataxia telangiectasia and the DNA-dependent protein kinase in the p53-mediated cellular response to ionising radiation. Oncogene 13: 1133–1138

  10. Kasten U, Plottner N, Johansen J, Overgaard J and Dikomey E (1999) Ku70/80 gene expression and DNA-dependent protein kinase (DNA-PK) activity do not correlate with double-strand break (dsb) repair capacity and cellular radiosensitivity in normal human fibroblasts. Br J Cancer 79: 1037–1041

  11. Kharbanda S, Pandey P, Jin S, Inoue S, Bharti A, Yuan ZM, Weichselbaum R, Weaver D and Kufe D (1997) Functional interaction between DNA-PK and c-Abl in response to DNA damage. Nature 386: 732–735

  12. Lambin P, Malaise EP and Joiner MC (1996) Might intrinsic radioresistance of human tumour cells be induced by radiation?. Int J Radiat Biol 69: 279–290

  13. Lees-Miller SP, Godbout R, Chan DW, Weinfeld M, Day RS 3rd, Barron GM and Allalunis-Turner J (1995) Absence of p350 subunit of DNA-activated protein kinase from a radiosensitive human cell line. Science 267: 1183–1185

  14. Marangoni E, Le Romancer M, Foray N, Muller C, Douc Rasy S, Barrois M, Calsou P, Bernier J, Eschwege F, Salles B and Bourhis J (2000) The transfer of an mRNA antisense of Ku86 increases the radiosensitivity of human transformed fibroblasts. Cancer Gene Ther,

  15. Marples B, Lambin P, Skov KA and Joiner MC (1997) Low dose hyperradiosensitivity and increased radioresistance in mammalian cells. Int J Radiat Biol 71: 721–735

  16. Muller C, Dusseau C, Calsou P and Salles B (1998) Human normal peripheral blood B-lymphocytes are deficient in DNA-dependent protein kinase activity due to the expression of a variant form of the Ku86 protein. Oncogene 16: 1553–1560

  17. Power MO (1997). PhD Thesis, University of London,

  18. Prasad AV, Mohan N, Chandrasekar B and Meltz ML (1995) Induction of transcription of ‘immediate early genes’ by low-dose ionizing radiation. Radiat Res 143: 263–272

  19. Shieh SY, Ikeda M, Taya Y and Prives C (1998) DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell 91: 325–334

  20. Short SC and Joiner MC (1998) Cellular response to low-dose irradiation. Clin Oncol 10: 73–77

  21. Short SC, Mayes C, Woodcock M, Johns H and Joiner MC (1999) Low dose hypersensitivity in the T98G human glioblastoma cell line. Int J Radiat Biol 75: 847–855

  22. Short SC (1999). PhD Thesis, University of London,

  23. Smith GCM and Jackson SP (1999) The DNA-dependent protein kinase. Genes Dev 13: 916–934

  24. Song Q, Lees-Miller SP, Kumar S, Zhang Z, Chan DW, Smith GC, Jackson SP, Alnemri ES, Litwack G, Khanna KK and Lavin MF (1996) DNA-dependent protein kinase catalytic subunit: a target for an ICE-like protease in apoptosis. EMBO J 15: 3238–3246

  25. Turesson Johansson KA, Nyman J, Flogegard M and Wahlgren T (1998) A clinical study on the effect of low dose per fraction. Radiother Oncol 48: S4–15

Download references

Author information

Rights and permissions

From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit

Reprints and Permissions

About this article

Cite this article

Vaganay-Juéry, S., Muller, C., Marangoni, E. et al. Decreased DNA-PK activity in human cancer cells exhibiting hypersensitivity to low-dose irradiation. Br J Cancer 83, 514–518 (2000) doi:10.1054/bjoc.2000.1258

Download citation


  • ionizing radiation
  • DNA repair
  • low-dose hyper-radiosensitivity
  • DNA-PK

Further reading