The regulation and functions of DNA and RNA G-quadruplexes.
TLDR
This Review discusses the identification of G4s and evidence for their formation in cells using chemical biology, imaging and genomic technologies, and discusses the connection between G4 formation and synthetic lethality in cancer cells, and recent progress towards considering G 4s as therapeutic targets in human diseases.Abstract:
DNA and RNA can adopt various secondary structures. Four-stranded G-quadruplex (G4) structures form through self-recognition of guanines into stacked tetrads, and considerable biophysical and structural evidence exists for G4 formation in vitro. Computational studies and sequencing methods have revealed the prevalence of G4 sequence motifs at gene regulatory regions in various genomes, including in humans. Experiments using chemical, molecular and cell biology methods have demonstrated that G4s exist in chromatin DNA and in RNA, and have linked G4 formation with key biological processes ranging from transcription and translation to genome instability and cancer. In this Review, we first discuss the identification of G4s and evidence for their formation in cells using chemical biology, imaging and genomic technologies. We then discuss possible functions of DNA G4s and their interacting proteins, particularly in transcription, telomere biology and genome instability. Roles of RNA G4s in RNA biology, especially in translation, are also discussed. Furthermore, we consider the emerging relationships of G4s with chromatin and with RNA modifications. Finally, we discuss the connection between G4 formation and synthetic lethality in cancer cells, and recent progress towards considering G4s as therapeutic targets in human diseases.read more
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References
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Quadruplex DNA: sequence, topology and structure
TL;DR: This survey focuses on the folding and structural features on quadruplexes formed from telomeric and non-telomeric DNA sequences, and examines fundamental aspects of topology and the emerging relationships with sequence.
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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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Crystal structure of parallel quadruplexes from human telomeric DNA.
TL;DR: This crystal structure of a quadruplex formed from four consecutive human telomeric DNA repeats and grown at a K+ concentration that approximates its intracellular concentration suggests a straightforward path for telomere folding and unfolding, as well as ways in which it can recognize telomerre-associated proteins.
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Quantitative visualization of DNA G-quadruplex structures in human cells
TL;DR: 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.
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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.