Human telomere, oncogenic promoter and 5′-UTR G-quadruplexes: diverse higher order DNA and RNA targets for cancer therapeutics

By Dinshaw J. Patel, A. Phan, V. Kuryavyi. Nucleic Acids Research, 2007

831 citations recorded by the source corpus.

Guanine-rich DNA sequences can form G-quadruplexes stabilized by stacked G–G–G–G tetrads in monovalent cation-containing solution. The length and number of individual G-tracts and the length and sequence context of linker residues define the diverse topologies adopted by G-quadruplexes. The review highlights recent solution NMR-based G-quadruplex structures formed by the four-repeat human telomere in K+ solution and the guanine-rich strands of c-myc, c-kit and variant bcl-2 oncogenic promoters, as well as a bimolecular G-quadruplex that targets HIV-1 integrase. Such structure determinations have helped to identify unanticipated scaffolds such as interlocked G-quadruplexes, as well as novel topologies represented by double-chain-reversal and V-shaped loops, triads, mixed tetrads, adenine-mediated pentads and hexads and snap-back G-tetrad alignments. The review also highlights the recent identification of guanine-rich sequences positioned adjacent to translation start sites in 5′-untranslated regions (5′-UTRs) of RNA oncogenic sequences. The activity of the enzyme telomerase, which maintains telomere length, can be negatively regulated through G-quadruplex formation at telomeric ends. The review evaluates progress related to ongoing efforts to identify small molecule drugs that bind and stabilize distinct G-quadruplex scaffolds associated with telomeric and oncogenic sequences, and outlines progress towards identifying recognition principles based on several X-ray-based structures of ligand–G-quadruplex complexes.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/57aa278090180e8f30a9ec268be40b40a5539f35

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Citations in the corpus

G-quadruplexes and their regulatory roles in biology (2015, background): “Intra-molecular folding requires the presence of four or more G-tracts in one strand, whereas inter-molecular folding can arise from two or four strands giving rise to parallel or antiparallel structures depending on the orientation of the strands in a G-quadruplex (4,5) (Figure 1B).”
Stability and kinetics of G-quadruplex structures (2008, background): “Many of the NMR analyses of quadruplexes have shown the existence of significant populations of alternative species (18,28,29,50), and they have been detected or assumed to be present by other spectroscopic or thermodynamic approaches (30,62,134,164–166).”
5′-UTR RNA G-quadruplexes: translation regulation and targeting (2012, background): “Another noteworthy difference is that whereas intramolecular DNA G-quadruplex structures are generally highly polymorphic (65,66), currently available biophysical data indicate that intramolecular RNA G-quadruplexes have a preference to adopt a parallel-stranded conformation regardless of the sequen”
Telomerase and cancer therapeutics (2008, background): “Small molecules that stabilize the possible G-quadruplex structure of telomere”