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Suppression of alternative telomere lengthening in cancer cells with reverse transcriptase inhibitors

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Abstract

Telomerase is a ribonucleoprotein enzyme that elongates telomeres and therefore maintains chromosomal stability in germ lines, as well as in the majority of cancer cells during cell doubling. However, up to 30% of human tumors of different types do not express telomerase but instead use an alternative lengthening of telomeres (ALT). Here we show that human tumor-derived ALT cell lines express a LINE-1 (L1) retrotransposon. This indicates its participation in telomere maintenance, possibly, by a slippage mechanism during telomeric DNA synthesis. Moreover, the suppression of L1-encoded reverse transcriptase activity by antisense strategy or treatment of ALT cells with reverse transcriptase inhibitor 3'-azido-2',3'-dideoxythymidine (AZT) induces progressive telomere shortening, arrest in G2 phase of the cell cycle, and, eventually, cancer cell death. This finding suggests a unique opportunity to cure cancer in a number of cases.

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Correspondence to V. Kh. Khavinson.

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Original Russian Text © I.E. Bondarev, V.Kh. Khavinson, 2016, published in Uspekhi Gerontologii, 2016, Vol. 29, No. 2, pp. 218–221.

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Bondarev, I.E., Khavinson, V.K. Suppression of alternative telomere lengthening in cancer cells with reverse transcriptase inhibitors. Adv Gerontol 6, 272–274 (2016). https://doi.org/10.1134/S2079057016040020

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  • DOI: https://doi.org/10.1134/S2079057016040020

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