title: Telomeric G-quadruplexes are a substrate and site of localization for human telomerase.
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.
authors.affiliation: Children's Medical Research Institute, University of Sydney, 214 Hawkesbury Road, Westmead, New South Wales 2145, Australia.
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Moye
authors.affiliation: Children's Medical Research Institute, University of Sydney, 214 Hawkesbury Road, Westmead, New South Wales 2145, Australia.
authors.forename: Karina C
authors.initials: KC
authors.lastname: Porter
authors.affiliation: Children's Medical Research Institute, University of Sydney, 214 Hawkesbury Road, Westmead, New South Wales 2145, Australia.
authors.forename: Scott B
authors.initials: SB
authors.lastname: Cohen
authors.affiliation: Commonwealth Scientific and Industrial Research Organisation, Manufacturing Flagship, 343 Royal Parade, Parkville, Victoria 3052, Australia.
authors.forename: Tram
authors.initials: T
authors.lastname: Phan
authors.affiliation: Children's Medical Research Institute, University of Sydney, 214 Hawkesbury Road, Westmead, New South Wales 2145, Australia.
authors.forename: Katherine G
authors.initials: KG
authors.lastname: Zyner
authors.affiliation: Children's Medical Research Institute, University of Sydney, 214 Hawkesbury Road, Westmead, New South Wales 2145, Australia.
authors.forename: Natsuki
authors.initials: N
authors.lastname: Sasaki
authors.affiliation: Commonwealth Scientific and Industrial Research Organisation, Manufacturing Flagship, 343 Royal Parade, Parkville, Victoria 3052, Australia.
authors.forename: George O
authors.initials: GO
authors.lastname: Lovrecz
authors.affiliation: School of Chemistry, University of Wollongong, Northfields Avenue, Wollongong, New South Wales 2522, Australia.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Beck
authors.affiliation: Children's Medical Research Institute, University of Sydney, 214 Hawkesbury Road, Westmead, New South Wales 2145, Australia.
authors.forename: Tracy M
authors.identifier: 0000000279905501
authors.initials: TM
authors.lastname: Bryan
mesh_terms: D015153:Blotting, Western; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D054856:G-Quadruplexes / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008652:Mesoporphyrins / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D019098:Telomerase / Q000378:metabolism*; D059505:Telomere Homeostasis
chemical_list: D008652:Mesoporphyrins; C065420:N-methylmesoporphyrin IX; D004247:DNA; C509186:TERT protein, human; D019098:Telomerase