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Repression of an alternative mechanism for lengthening of telomeres in somatic cell hybrids

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Abstract

Some immortalized cell lines maintain their telomeres in the absence of detectable telomerase activity by an alternative (ALT) mechanism. To study how telomere maintenance is controlled in ALT cells, we have fused an ALT cell line GM847 (SV40 immortalized human skin fibroblasts) with normal fibroblasts or with telomerase positive immortal human cell lines and have examined their proliferative potential and telomere dynamics. The telomeres in ALT cells are characteristically very heterogeneous in length, ranging from very short to very long. The ALT×normal hybrids underwent a rapid reduction in telomeric DNA and entered a senescence-like state. Immortal segregants rapidly reverted to the ALT telomere phenotype. Fusion of ALT cells to telomerase-positive immortal cells in the same immortalization complementation group resulted in hybrids that appeared immortal and also exhibited repression of the ALT telomere phenotype. In these hybrids, which were all telomerase-positive, we observed an initial rapid loss of most long telomeres, followed either by gradual loss of the remaining long telomeres at a rate similar to the rate of telomere shortening in normal telomerase-negative cells, or by maintenance of shortened telomeres. These data indicate the existence of a mechanism of rapid telomere deletion in human cells. They also demonstrate that normal cells and at least some telomerase-positive immortal cells contain repressors of the ALT telomere phenotype.

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Acknowledgements

The authors thank Dr Peter Rowe for his comments on the manuscript. These studies were supported by a project grant from the National Health and Medical Research Council of Australia, and the Carcinogenesis Fellowship of the New South Wales Cancer Council.

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Author notes

  1. Tracy M Bryan

    Present address: Department of Chemistry and Biochemistry, Campus Box 215, HHMI, University of Colorado, Boulder, CO, 80309-0215, USA

  2. Torben Hackl

    Present address: Institute of Cell Biology, University of Witten/Herdecke, Stockumer Strasse 10, 58448, Witten, Germany

Authors and Affiliations

  1. Cancer Research Group, Children's Medical Research Institute, 214 Hawkesbury Road, Westmead, NSW 2145, Sydney, Australia

    Kilian Perrem, Tracy M Bryan, Anna Englezou, Torben Hackl, Elsa L Moy & Roger R Reddel

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  1. Kilian Perrem
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  2. Tracy M Bryan
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Perrem, K., Bryan, T., Englezou, A. et al. Repression of an alternative mechanism for lengthening of telomeres in somatic cell hybrids. Oncogene 18, 3383–3390 (1999). https://doi.org/10.1038/sj.onc.1202752

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