Telomeric G-quadruplexes are a substrate and site of localization for human telomerase
Aaron L. Moye,
Karina C. Porter,
Scott B. Cohen,
Tram Phan,
Katherine G. Zyner,
Natsuki Sasaki,
George O. Lovrecz,
Jennifer L. Beck and
Tracy M. Bryan ()
Additional contact information
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
Nature Communications, 2015, vol. 6, issue 1, 1-12
Abstract:
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.
Date: 2015
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8643
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DOI: 10.1038/ncomms8643
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