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DNA damage transiently increases TRF2 mRNA expression and telomerase activity

Leukemia volume 17, pages 2007–2015 (2003)Cite this article

Abstract

Telomerase activity transiently increases when HL60 cells are treated with the topoisomerase II inhibitor etoposide. A quantitative assessment revealed that telomerase is activated by etoposide treatment in a number of cell lines and that the increase is reversible after withdrawal of etoposide from the cell culture. Telomerase activation correlated with the occurrence of DNA damage but not with cell cycle arrest. We did not detect any transcriptional upregulation of hTERT mRNA, suggesting a post-transcriptional mechanism of telomerase activation. Furthermore, the mRNA expression of the telomere binding protein TRF2 was upregulated early and reversibly after etoposide treatment. TRF1 mRNA expression levels were unchanged after DNA damage, but increased when the cells accumulated in the G2/M phase. The data show that the telosome reacts after DNA damage by upregulating telomerase activity and TRF2 expression in malignant cells. It has previously been shown that overexpression of TRF2 can repress senescence signals arising from critically shortened telomeres. We show here that TRF2 is upregulated by undirected DNA damage that also affects the telomeric DNA. These data suggest that upregulation of telomerase activity and TRF2 expression might act as antiapoptotic mechanisms in the DNA-damage response of malignant cells.

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Acknowledgements

We thank M Hauberg for her help with immunohistochemistry and E Dege for critically reading the manuscript. This work was supported in part by the ‘Kinder Krebs Initiative Buchholz-Seppensen-Holm’, Germany.

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Authors and Affiliations

  1. Department of Hematopathology and Lymph Node Registry Kiel, Niemannsweg Kiel, Germany

    W Klapper, W Qian, C Schulte & R Parwaresch

  2. Department of Hematology, First affiliated Hospital of Zhejiang University, Hangzhou, China

    W Qian

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Klapper, W., Qian, W., Schulte, C. et al. DNA damage transiently increases TRF2 mRNA expression and telomerase activity. Leukemia 17, 2007–2015 (2003). https://doi.org/10.1038/sj.leu.2403086

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