Quantitative visualization of DNA G-quadruplex structures in human cells
TLDR
It is shown explicitly that G-quadruplex formation in DNA is modulated during cell-cycle progression and that endogenous G- quadruplex DNA structures can be stabilized by a small-molecule ligand and corroborate the application of stabilizing ligands in a cellular context to target G- Quadruplexes and intervene with their function.Abstract:
Four-stranded G-quadruplex nucleic acid structures are of great interest as their high thermodynamic stability under near-physiological conditions suggests that they could form in cells. Here we report the generation and application of an engineered, structure-specific antibody employed to quantitatively visualize DNA G-quadruplex structures in human cells. We show explicitly that G-quadruplex formation in DNA is modulated during cell-cycle progression and that endogenous G-quadruplex DNA structures can be stabilized by a small-molecule ligand. Together these findings provide substantive evidence for the formation of G-quadruplex structures in the genome of mammalian cells and corroborate the application of stabilizing ligands in a cellular context to target G-quadruplexes and intervene with their function.read more
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Electrochemical Sensors and Biosensors Based on Nanomaterials and Nanostructures
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G-quadruplexes and their regulatory roles in biology.
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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.
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C9orf72 nucleotide repeat structures initiate molecular cascades of disease
Aaron R. Haeusler,Christopher J. Donnelly,Goran Periz,Eric A J Simko,Patrick G. Shaw,Min-Sik Kim,Nicholas J. Maragakis,Juan C. Troncoso,Akhilesh Pandey,Rita Sattler,Jeffrey D. Rothstein,Jiou Wang +11 more
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High-throughput sequencing of DNA G-quadruplex structures in the human genome
Vicki S Chambers,Giovanni Marsico,Jonathan Mark Boutell,Marco Di Antonio,Geoffrey Paul Smith,Shankar Balasubramanian +5 more
TL;DR: A high-resolution sequencing–based method is presented to detect G4s in the human genome and observed a high G4 density in functional regions, as well as in genes previously not predicted to contain these structures (such as BRCA2).
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DNA G-quadruplexes in the human genome: detection, functions and therapeutic potential.
TL;DR: Advances in the detection and mapping of G4 structures in the human genome and in biologically relevant contexts provide important new insights into the functions of G 4 structures in, for example, the regulation of transcription and genome stability, and uncover their potential relevance for cancer therapy.
References
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Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription.
TL;DR: The principle that c-MYC transcription can be controlled by ligand-mediated G-quadruplex stabilization is established, establishing the principle that the purine-rich strand of the DNA in this region can form two different intramolecular G- quadruplex structures.
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Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosis
Dipankar Sen,Walter Gilbert +1 more
TL;DR: It is speculated that this self-recognition of guanine-rich motifs of DNA serves to bring together, and to zipper up in register, the four homologous chromatids during meiosis.
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Prevalence of quadruplexes in the human genome
TL;DR: There is a significant repression of quadruplexes in the coding strand of exonic regions, which suggests that quadruplex-forming patterns are disfavoured in sequences that will form RNA.
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Highly prevalent putative quadruplex sequence motifs in human DNA
TL;DR: Using arithmetic ratio and probability techniques, frequent and systematic occurrence of certain sequence types are discovered, the most prominent being a potential quadruplex containing CCTGT in the first ‘loop’ position.
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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.