Article
- The EMBO Journal (2006) 25, 1148 - 1159
- doi:10.1038/sj.emboj.7601006
Published online: 2 March 2006
Subject Category:
Extension of G-quadruplex DNA by ciliate telomerase
Liana Oganesian1, Ian K Moon2, Tracy M Bryan1 and Michael B Jarstfer2
- Children's Medical Research Institute, Sydney, Australia
- School of Pharmacy, Division of Medicinal Chemistry and Natural Products, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Correspondence to:
Tracy M Bryan, Children's Medical Research Institute, 214 Hawkesbury Road, Westmead, Sydney, NSW 2145, Australia. Tel.: +61 2 9687 2800; Fax: +61 2 9687 2120; E-mail: tbryan@cmri.usyd.edu.au
Michael B Jarstfer, School of Pharmacy, Division of Medicinal Chemistry and Natural Products, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7360, USA. Tel.: +1 919 966 6422; Fax: +1 919 966 0204; E-mail: jarstfer@email.unc.edu
Received 2 September 2005; Accepted 25 January 2006
Abstract
Telomeric DNA can fold into four-stranded structures known as G-quadruplexes. Here we investigate the ability of G-quadruplex DNA to serve as a substrate for recombinant Tetrahymena and native Euplotes telomerase. Inter- and intramolecular G-quadruplexes were gel-purified and their stability examined using native gel electrophoresis, circular dichroism (CD) and thermal denaturation. While intermolecular G-quadruplexes were highly stable, they were excellent substrates for both ciliate telomerases in primer extension assays. In contrast, intramolecular G-quadruplexes formed in K+ exhibited biphasic unfolding and were not extended by ciliate telomerases. Na+-stabilised intramolecular G-quadruplexes were extended by telomerase owing to their rapid rate of dissociation. The Tetrahymena telomerase protein component bound to inter- but not intramolecular K+-stabilised G-quadruplexes. This study provides evidence that parallel intermolecular G-quadruplexes can serve as substrates for telomerase in vitro, their extension being mediated through direct interactions between this higher-order structure and telomerase.
Keywords:
- ciliate,
- G-quadruplex,
- telomerase,
- telomere
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