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Subnuclear shuttling of human telomerase induced by transformation and DNA damage

Nature Cell Biology volume 4, pages 731–736 (2002)Cite this article

Abstract

The telomerase ribonucleoprotein complex caps chromosome ends by adding telomeric repeats. Here we show that catalytically active human telomerase has a regulated intranuclear localization that is dependent on the cell-cycle stage, transformation and DNA damage. In primary cell lines, low expression of a fusion protein of green fluorescent protein and telomerase reverse transcriptase (GFP–hTERT) increases telomerase activity and stabilizes the maintenance of telomere length. Confocal microscopy shows that the release of telomerase to the nucleoplasm from sequestration at nucleolar sites is enhanced at the expected time of telomere replication. By contrast, in tumour and transformed cells, there is an almost complete dissociation of telomerase from nucleoli at all stages of the cell cycle. Transfection of the simian virus 40 genome into a primary cell line is sufficient to mobilize telomerase from nucleoli to the nucleoplasm. Conversely, ionizing radiation induces the reassociation of telomerase with nucleoli in both primary and transformed cells. These findings show that transformation and DNA damage have opposite effects on the cellular regulation of active telomerase, affecting the enzyme's access to both telomeric and nontelomeric substrates.

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Figure 1: Expression of GFP–hTERT in human fibroblasts.
Figure 2: Cell-cycle-dependent association of GFP–hTERT with nucleoli in primary cells.
Figure 3: Nucleolar exclusion pattern of GFP–hTERT in transformed cells.
Figure 4: Conversion of telomerase nucleolar association to nucleolar exclusion without crisis.
Figure 5: Enhanced nucleolar association after DNA damage.

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Acknowledgements

We thank D. Schichnes, S. Ruzin and H. Nolla for technical help; P. Kaminker, J. Campisi, J. Shay, W. Wright and M. Botchan for reagents; and members of the Collins laboratory for discussion and comments.

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Authors and Affiliations

  1. Department of Molecular and Cell Biology, University of California, Berkeley, 94720-3204, California, USA

    Judy M. Y. Wong, Leonard Kusdra & Kathleen Collins

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  1. Judy M. Y. Wong
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  2. Leonard Kusdra
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  3. Kathleen Collins
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Correspondence to Kathleen Collins.

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Wong, J., Kusdra, L. & Collins, K. Subnuclear shuttling of human telomerase induced by transformation and DNA damage. Nat Cell Biol 4, 731–736 (2002). https://doi.org/10.1038/ncb846

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