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Protection of internal (TTAGGG)n repeats in Chinese hamster cells by telomeric protein TRF1

Oncogene volume 22, pages 6690–6698 (2003)Cite this article

Abstract

Chinese hamster cells have large interstitial (TTAGGG) bands (ITs) which are unstable and should be protected by an unknown mechanism. Here, we expressed in Chinese hamster V79 cells green fluorescent protein (GFP)-tagged human TRF1, and found that a major fraction of GFP-TRF1 bound to ITs is diffusionally mobile. This fraction strongly decreases after treatment of cells with wortmannin, a protein kinase inhibitor, and this drug also increases the frequency of chromosome aberrations. Ionizing radiation does not induce detectable translocation of GFP-TRF1 to the sites of random double-strand breaks visualized using antibodies against histone γ-H2AX. TRF1 is known to be eliminated from telomeres by overexpression of tankyrase 1 which induces TRF1 poly(ADP-ribosyl)ation. We transfected V79 cells by plasmid encoding tankyrase 1 and found that the frequency of chromosome rearrangements is increased in these cells independently of their treatment by IR. Taken together, our results suggest that TRF1 is involved in sequence-specific protection of internal nontelomeric (TTAGGG)n repeats.

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Abbreviations

ATM:

Ataxia teleangiectasia-mutated protein

CA:

chromosome aberration

DSB:

double-strand DNA break

GFP:

green fluorescent protein

IT:

internal non-telomeric blocks of (TTAGGG)n sequences

NHEJ:

nonhomologous end-joining

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Acknowledgements

We thank S Smith for her kind gift of plasmids pTetFLNLS and pUHR15-1. This research was supported by the Office of Science (BER), US Department of Energy, Grant No. DE-FG03-01ER63070, by the National Institutes of Health Grant No. 5R01-HD39830-02, by the Deutsche Forschung Gemeinschaft Grant 436 RUS113/126/0, by the Civilian Research and Development Foundation Grant ST-012-0 and the Russian Fund for Basic Research Grants 01-04-49486 and 02-04-49145.

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Authors and Affiliations

  1. Laboratory of Chromosome Stability, Institute of Cytology, Russian Academy of Sciences, 194064 St, Petersburg, Russia

    Raisa Ivanovna Krutilina, Alexandra Nikolaevna Smirnova, Olga Stanislavovna Mudrak, Nadezhda Mikhailovna Pleskach, Maria Pavlovna Svetlova & Nikolai Viktorovich Tomilin

  2. Institute of Biochemistry, Free University of Berlin, Thielallee 63, Berlin-Dahlem, 14195, Germany

    Shiao-Li Oei

  3. Department of Biological Chemistry, UC Davis School of Medicine, Davis, 95616, CA, USA

    Peter M Yau, Edwin Morton Bradbury & Andrey Olegovich Zalensky

  4. Bioscience Division, MSM 888, Los Alamos National Laboratory, Los Alamos, 87545, NM, USA

    Edwin Morton Bradbury

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  1. Raisa Ivanovna Krutilina
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  2. Alexandra Nikolaevna Smirnova
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  3. Olga Stanislavovna Mudrak
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  4. Nadezhda Mikhailovna Pleskach
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Correspondence to Nikolai Viktorovich Tomilin.

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Krutilina, R., Smirnova, A., Mudrak, O. et al. Protection of internal (TTAGGG)n repeats in Chinese hamster cells by telomeric protein TRF1. Oncogene 22, 6690–6698 (2003). https://doi.org/10.1038/sj.onc.1206745

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