Small-molecule-mediated G-quadruplex isolation from human cells.
Nucleic acids containing stretches of tandem guanines can fold into four-stranded structures called G-quadruplexes. The existence of such sequences in genomic DNA suggests the occurrence of these motifs in cells, with potential implications in a number of biological processes relevant to cancer. Small molecules have proven to be valuable tools to dissect cell circuitry. Here, we describe a synthetic small molecule derived from an N,N'-bis(2-quinolinyl)pyridine-2,6-dicarboxamide, which is designed to mediate the selective isolation of G-quadruplex nucleic acids. The methodology was successfully applied to a range of DNA and RNA G-quadruplexes in vitro. We demonstrate the general applicability of the method by isolating telomeric DNA-containing G-quadruplex motifs from cells. We show that telomeres are targets for the probe, providing further evidence of the formation of G-quadruplexes in human cells.
Department of Chemistry, The University of Cambridge, Cambridge CB2 1EW, UK.
Sebastian
S
Müller
Sunita
S
Kumari
Raphaël
R
Rodriguez
Shankar
S
Balasubramanian
D000577:Amides / Q000737:chemistry; D000634:Aminoquinolines / Q000737:chemistry*; D001710:Biotin / Q000031:analogs & derivatives* / Q000737:chemistry; D045744:Cell Line, Tumor; D004247:DNA / Q000302:isolation & purification; D054856:G-Quadruplexes; D006801:Humans; D016615:Telomere / Q000737:chemistry
D000577:Amides; D000634:Aminoquinolines; D001710:Biotin; D004247:DNA