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

Authors

Aaron L. Moye, University of Sydney
Karina C. Porter, University of Sydney
Scott Cohen, University of Sydney
Tram Phan, CSIRO Manufacturing Flagship
Katherine G. Zyner, University of Sydney
Natsuki Sasaki, University of Sydney
George Lovrecz, CSIRO Manufacturing Flagship
Jennifer L. Beck, University of WollongongFollow
Tracy Bryan, University of Sydney

RIS ID

101962

Publication Details

Moye, A. L., Porter, K. C., Cohen, S. B., Phan, T., Zyner, K. G., Sasaki, N., Lovrecz, G. O., Beck, J. L. & Bryan, T. M. (2015). Telomeric G-quadruplexes are a substrate and site of localization for human telomerase. Nature Communications, 6 (July), 7643-1 - 7643-12.

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.