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Cellular stress triggers the human topoisomerase I damage response independently of DNA damage in a p53 controlled manner

Oncogene volume 26, pages 123–131 (2007)Cite this article

Abstract

The ‘human topoisomerase I (htopoI) damage response’ was reported to be triggered by various kinds of DNA lesions. Also, a high and persistent level of htopoI cleavage complexes correlated with apoptosis. In the present study, we demonstrate that DNA damage-independent induction of cell death using colcemid and tumor necrosis factor α is also accompanied by a strong htopoI response that correlates with the onset of apoptotic hallmarks. Consequently, these results suggest that htopoI cleavage complex formation may be caused by signaling pathways independent of the kind of cellular stress. Thus, protein interactions or signaling cascades induced by DNA damage or cellular stress might lead to the formation of stabilized cleavage complexes rather than the DNA lesion itself. Finally, we show that p53 not only plays a key role in the regulation of the htopoI response to UV-C irradiation but also to treatment with colcemid.

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References

  • Aruoma OI, Halliwell B, Hoey BM, Butler J . (1989). Free Radic Biol Med 6: 593–597.

  • Bradford M . (1976). Anal Biochem 72: 248–254.

  • Casciola-Rosen L, Anhalt G, Rosen A . (1995). J Exp Med 181: 1557–1561.

  • Champoux JJ . (2001). Annu Rev Biochem 70: 369–413.

  • Chen X, Ko LJ, Jayaraman L, Prives C . (1996). Genes Dev 10: 2438–2451.

  • Daroui P, Desai SD, Li TK, Liu AA, Liu LF . (2004). J Biol Chem 279: 14587–14594.

  • Hsiang YH, Hertzberg R, Hecht S, Liu LF . (1985). J Biol Chem 260: 14873–14878.

  • Huppertz B, Frank HG, Kaufmann P . (1999). Anat Embryol (Berlin) 200: 1–18.

  • Janicke RU, Sprengart ML, Wati MR, Porter AG . (1998). J Biol Chem 273: 9357–9360.

  • Kaufmann SH, Desnoyers S, Ottaviano Y, Davidson NE, Poirier GG . (1993). Cancer Res 53: 3976–3985.

  • Lanza A, Tornaletti S, Rodolfo C, Scanavini M, Pedrini A . (1996). J Biol Chem 271: 6978–6986.

  • Li TK, Liu LF . (2001). Annu Rev Pharmacol Toxicol 41: 53–77.

  • Mao Y, Muller MT . (2003). DNA Repair (Amsterdam) 2: 1115–1126.

  • Mao Y, Okada S, Chang L, Muller M . (2000). Cancer Res 60: 4538–4543.

  • Pommier Y, Kohlhagen G, Laco GS, Kroth H, Sayer JM, Jerina DM . (2002). J Biol Chem 277: 13666–13672.

  • Pommier Y, Kohlhagen G, Pourquier P, Sayer J, Kroth H, Jerina D . (2000). Proc Natl Acad Sci USA 97: 2040–2045.

  • Pourquier P, Bjornsti M, Pommier Y . (1998). J Biol Chem 273: 27245–27249.

  • Pourquier P, Gioffre C, Kohlhagen G, Urasaki Y, Goldwasser F, Hertel L et al. (2002). Clin Cancer Res 8: 2499–2504.

  • Pourquier P, Pilon A, Kohlhagen G, Mazumder A, Sharma A, Pommier Y . (1997a). J Biol Chem 272: 26441–26447.

  • Pourquier P, Takebayashi Y, Urasaki Y, Gioffre C, Kohlhagen G, Pommier Y . (2000). Proc Natl Acad Sci USA 97: 1885–1890.

  • Pourquier P, Ueng L, Fertala J, Wang D, Park H, Essigmann J et al. (1999). J Biol Chem 274: 8516–8523.

  • Pourquier P, Ueng L, Kohlhagen G, Mazumder A, Gupta M, Kohn K et al. (1997b). J Biol Chem 272: 7792–7796.

  • Pourquier P, Waltman J, Urasaki Y, Loktionova N, Pegg A, Nitiss J et al. (2001). Cancer Res 61: 53–58.

  • Salvesen GS, Dixit VM . (1997). Cell 91: 443–446.

  • Samejima K, Svingen P, Basi G, Kottke T, Mesner PJ, Stewart L et al. (1999). J Biol Chem 274: 4335–4340.

  • Sherwood SW, Sheridan JP, Schimke RT . (1994). Exp Cell Res 215: 373–379.

  • Soe K, Rockstroh A, Schache P, Grosse F . (2004). DNA Repair (Amsterdam) 3: 387–393.

  • Sordet O, Khan QA, Plo I, Pourquier P, Urasaki Y, Yoshida A et al. (2004a). J Biol Chem 279: 50499–50504.

  • Sordet O, Liao Z, Liu H, Antony S, Stevens EV, Kohlhagen G et al. (2004b). J Biol Chem 279: 33968–33975.

  • Stewart A, Herrera R, Nordheim A . (1990). Cell 60: 141–149.

  • Subramanian D, Rosenstein B, Muller M . (1998). Cancer Res 58: 976–984.

  • Wajant H, Pfizenmaier K, Scheurich P . (2003). Cell Death Differ 10: 45–65.

  • Wolf BB, Schuler M, Echeverri F, Green DR . (1999). J Biol Chem 274: 30651–30656.

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Acknowledgements

We are grateful to Dr Carol Prives (Columbia University, NY, USA) for providing us with the H1299-TOFF-p53 cell line. This work was supported by grant Gr 895/15-1/2 of the ‘Deutsche Forschungsgemeinschaft’.

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  1. A Kleinert

    Present address: Friedrich Miescher Institute, Maulbeerstr. 66, CH-4058, Basel, Switzerland

Authors and Affiliations

  1. Leibniz Institute for Age Research – Fritz-Lipmann-Institute eV, Biochemistry, Jena, Germany

    A Rockstroh, A Kleinert, M Kramer, F Grosse & K Søe

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  1. A Rockstroh
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  3. M Kramer
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Correspondence to K Søe.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc).

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Rockstroh, A., Kleinert, A., Kramer, M. et al. Cellular stress triggers the human topoisomerase I damage response independently of DNA damage in a p53 controlled manner. Oncogene 26, 123–131 (2007). https://doi.org/10.1038/sj.onc.1209766

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