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Telomeric G-quadruplexes are a substrate and site of localization for human telomerase

Author

Listed:
  • Aaron L. Moye

    (Children’s Medical Research Institute, University of Sydney)

  • Karina C. Porter

    (Children’s Medical Research Institute, University of Sydney)

  • Scott B. Cohen

    (Children’s Medical Research Institute, University of Sydney)

  • Tram Phan

    (Commonwealth Scientific and Industrial Research Organisation, Manufacturing Flagship)

  • Katherine G. Zyner

    (Children’s Medical Research Institute, University of Sydney)

  • Natsuki Sasaki

    (Children’s Medical Research Institute, University of Sydney)

  • George O. Lovrecz

    (Commonwealth Scientific and Industrial Research Organisation, Manufacturing Flagship)

  • Jennifer L. Beck

    (School of Chemistry, University of Wollongong, Northfields Avenue, Wollongong, New South Wales 2522, Australia)

  • Tracy M. Bryan

    (Children’s Medical Research Institute, University of Sydney)

Abstract

It has been hypothesized that G-quadruplexes can sequester the 3′ end of the telomere and prevent it from being extended by telomerase. Here we purify and characterize stable, conformationally homogenous human telomeric G-quadruplexes, and demonstrate that human telomerase is able to extend parallel, intermolecular conformations in vitro. These G-quadruplexes align correctly with the RNA template of telomerase, demonstrating that at least partial G-quadruplex resolution is required. A highly purified preparation of human telomerase retains this extension ability, establishing that the core telomerase enzyme complex is sufficient for partial G-quadruplex resolution and extension. The parallel-specific G-quadruplex ligand N-methyl mesoporphyrin IX (NMM) causes an increase in telomeric G-quadruplexes, and we show that telomerase colocalizes with a subset of telomeric G-quadruplexes in vivo. The ability of telomerase to partially unwind, extend and localize to these structures implies that parallel telomeric G-quadruplexes may play an important biological role.

Suggested Citation

  • Aaron L. Moye & Karina C. Porter & Scott B. Cohen & Tram Phan & Katherine G. Zyner & Natsuki Sasaki & George O. Lovrecz & Jennifer L. Beck & Tracy M. Bryan, 2015. "Telomeric G-quadruplexes are a substrate and site of localization for human telomerase," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8643
    DOI: 10.1038/ncomms8643
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