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Inhibition of telomerase by G-quartet DMA structures

Nature volume 350, pages 718–720 (1991)Cite this article

Abstract

THE ends or telomeres of the linear chromosomes of eukaryotes are composed of tandem repeats of short DNA sequences, one strand being rich in guanine (G strand) and the complementary strand in cytosine1,2. Telomere synthesis involves the addition of telomeric repeats to the G strand by telomere terminal transferase (telomerase)3–6. Telomeric G-strand DNAs from a variety of organisms adopt compact structures7, the most stable of which is explained by the formation of G-quartets8,9. Here we investigate the capacity of the different folded forms of telomeric DNA to serve as primers for the Oxytricha nova telomerase in vitro. Formation of the K+-stabilized G-quartet structure in a primer inhibits its use by telomerase. Furthermore, the octanucleotide T4G4, which does not fold, is a better primer than (T4G4)2, which can form a foldback structure7–10. We conclude that telomerase does not require any folding of its DNA primer. Folding of telomeric DNA into G-quartet structures seems to influence the extent of telomere elongation in vitro and might therefore act as a negative regulator of elongation in vivo.

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Author notes

  1. Alan M. Zahler

    Present address: Fred Hutchinson Cancer Research Center, Seattle, Washington, 98104, USA

  2. James R. Williamson

    Present address: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA

Authors and Affiliations

  1. Department of Molecular, Cellular and Developmental Biology, Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of Colorado, Boulder, Colorado, 80309–0215, USA

    Alan M. Zahler, James R. Williamson, Thomas R. Cech & David M. Prescott

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  1. Alan M. Zahler
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  2. James R. Williamson
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  3. Thomas R. Cech
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  4. David M. Prescott
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Zahler, A., Williamson, J., Cech, T. et al. Inhibition of telomerase by G-quartet DMA structures. Nature 350, 718–720 (1991). https://doi.org/10.1038/350718a0

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