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Telomere maintenance by recombination in human cells

Nature Genetics volume 26, pages 447–450 (2000)Cite this article

Abstract

Telomeres of eukaryotic chromosomes contain many tandem repeats of a G-rich sequence (for example, TTAGGG in vertebrates1). In most normal human cells, telomeres shorten with each cell division, and it is proposed that this limits the number of times these cells can replicate2. Telomeres may be maintained in germline cells, and in many immortalized cells and cancers, by the telomerase holoenzyme3 (first discovered in the ciliate Tetrahymena4), which uses an RNA subunit as template for synthesis of telomeric DNA by the reverse transcriptase catalytic subunit5. Some immortalized human cell lines and some tumours maintain their telomeres in the absence of any detectable telomerase activity by a mechanism referred to as alternative lengthening of telomeres6,7 (ALT). Here we show that DNA sequences are copied from telomere to telomere in an immortalized human ALT cell line, indicating that ALT occurs by means of homologous recombination and copy switching.

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Figure 1: Strategy for detecting inter-telomeric copying of DNA.
Figure 2: Detection of plasmid tag DNA at the telomere by FISH.
Figure 3: Southern-blot analysis of GM847 and HT1080 lines.
Figure 4: Transfer of a single tagged telomere into GM847 cells.

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Acknowledgements

We thank T. Haaf for the panel of subtelomeric CEPH mega-YACs, and T. de Lange for plasmid pSXneo-1.6-T2AG3. Supported by a project grant from the National Health and Medical Research Council of Australia, the Carcinogenesis Fellowship of the New South Wales Cancer Council, and a scholarship of the Judith Hyam Memorial Trust Fund for Cancer Research.

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Authors and Affiliations

  1. Cancer Research Unit, Children's Medical Research Institute , Westmead, Sydney, Australia

    Melissa A. Dunham, Axel A. Neumann, Clare L. Fasching & Roger R. Reddel

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  1. Melissa A. Dunham
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  2. Axel A. Neumann
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  3. Clare L. Fasching
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  4. Roger R. Reddel
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Correspondence to Roger R. Reddel.

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Dunham, M., Neumann, A., Fasching, C. et al. Telomere maintenance by recombination in human cells. Nat Genet 26, 447–450 (2000). https://doi.org/10.1038/82586

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