Human telomere, oncogenic promoter and 5′-UTR G-quadruplexes: diverse higher order DNA and RNA targets for cancer therapeutics
TLDR
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.Abstract:
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.read more
Citations
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Journal ArticleDOI
DNA secondary structures: stability and function of G-quadruplex structures
TL;DR: This Review focuses on emerging evidence relating to the characteristics of G-quadruplex structures and the possible influence of such structures on genomic stability and cellular processes, such as transcription.
Journal ArticleDOI
G-quadruplexes and their regulatory roles in biology.
Daniela Rhodes,Hans J. Lipps +1 more
TL;DR: Recent evidence for the in vivo presence and function of DNA and RNA G-quadruplexes in various cellular pathways including DNA replication, gene expression and telomere maintenance is summarized.
Journal ArticleDOI
G-quadruplex structures: in vivo evidence and function
Hans J. Lipps,Daniela Rhodes +1 more
TL;DR: Recent studies aimed at uncovering the in vivo presence and function of G-quadruplexes in genomes and RNA are reviewed, with a particular focus on telomeric G- quadruplexe and how their formation and resolution is regulated to permit telomere synthesis.
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A hitchhiker's guide to G-quadruplex ligands
TL;DR: The present article aims to help researchers enter this exciting research field, and to highlight recent advances in the design of G-quadruplex ligands.
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Telomerase and cancer therapeutics
TL;DR: The prospect of adding telomerase-based therapies to the growing list of new anticancer products is promising, but what are the advantages and limitations of different approaches, and which patients are the most likely to respond?
References
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TL;DR: Bcl-2 and related cytoplasmic proteins are key regulators of apoptosis, the cell suicide program critical for development, tissue homeostasis, and protection against pathogens.
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TL;DR: It is proposed that the novel telomere terminal transferase is involved in the addition of telomeric repeats necessary for the replication of chromosome ends in eukaryotes.
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Friedreich's Ataxia: Autosomal Recessive Disease Caused by an Intronic GAA Triplet Repeat Expansion
Victoria Campuzano,Laura Montermini,María Dolores Moltó,Luigi Pianese,Mireille Cossée,F Cavalcanti,Eugenia Monros,François Rodius,Franck Duclos,Antonella Monticelli,Federico Zara,Joaquín Cañizares,Hana Koutnikova,Sanjay I. Bidichandani,Cinzia Gellera,Alexis Brice,Paul Trouillas,Giuseppe De Michele,Alessandro Filla,Rosa de Frutos,Francisco Palau,Pragna Patel,Stefano Di Donato,Jean-Louis Mandel,Sergio Cocozza,Michel Koenig,Massimo Pandolfo +26 more
TL;DR: A few FRDA patients were found to have point mutations in X25, but the majority were homozygous for an unstable GAA trinucleotide expansion in the first X25 intron.