title: Deciphering the DNAzyme activity of multimeric quadruplexes: insights into their actual role in the telomerase activity evaluation assay.
abstract: The end of human telomeres is comprised of a long G-rich single-stranded DNA (known as 3'-overhang) able to adopt an unusual three-dimensional "beads-on-the-string" organization made of consecutively stacked G-quadruplex units (so-called quadruplex multimers). It has been widely demonstrated that, upon interaction with hemin, discrete quadruplexes acquire peroxidase-mimicking properties, oxidizing several organic probes in H(2)O(2)-rich conditions; this property, known as DNAzyme, has found tens of applications in the last two decades. However, little is known about the DNAzyme activity of multimeric quadruplexes; this is an important question to address, especially in light of recent reports that exploit the DNAzyme process to optically assess the activity of an enzyme that elongates the telomeric overhang, the telomerase. Herein, we thoroughly investigate the DNAzyme activity of long telomeric fragments, with a particular focus on both the nature of the hemin/multimeric quadruplex interactions and the putative higher-order fold of the studied fragments; in light of our results, we also propose possible ways that may be followed to improve the use of DNAzyme to evaluate the telomerase activity.
authors: Institut de Chimie Moléculaire, Université de Bourgogne (ICMUB), CNRS UMR5260, 9, avenue Alain Savary, 21000 Dijon, France.
authors: Loic
authors: L
authors: Stefan
authors: Franck
authors: F
authors: Denat
authors: David
authors: D
authors: Monchaud
mesh_terms: D001665:Binding Sites; D021881:DNA, Catalytic / Q000378:metabolism*; D054856:G-Quadruplexes; D006427:Hemin / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism*
chemical_list: D021881:DNA, Catalytic; D006427:Hemin; D019098:Telomerase