Quantitative Visualization of DNA G-quadruplex Structures in Human Cells

By Giulia Biffi, D. Tannahill, J. McCafferty, Shankar Balasubramanian. Nature Chemistry, 2013

1,919 citations recorded by the source corpus.

Four-stranded G-quadruplex nucleic acid structures have been 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 that was employed to visualize quantitatively DNA G-quadruplex structures in human cells. We explicitly show 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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/4bbfc6aaa24924fa6756b07ce4da37be97f3d853

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In Molecular Biology

1. D. Rhodes
2. H. Lipps
3. Jochen Spiegel
4. Santosh Adhikari
5. Shankar Balasubramanian
6. S. Harteis
7. S. Schneider

Citations in the corpus

• The Structure and Function of DNA G-Quadruplexes (2020, background): “structures in human cell lines upon ligand treatment together with depletion of the G4 resolving helicase FANCJ [41,42], to reveal increased numbers of G4 foci staining in nuclei after pyridostatin [41] or telomestatin ligand treatment and FANCJ depletion in chicken DT40 cells [42].”
• Making the Bend: DNA Tertiary Structure and Protein-DNA Interactions (2014, background): “of quadruplexes in eukaryotes is modulated in the course of DNA replication [71].”
• G-quadruplexes and their regulatory roles in biology (2015, background): “The regulation of G-quadruplex formation through the cell cycle has been shown for ciliates and human cells (66,78), but it would be most insightful to know their occurrence and location during cellular differentiation to understand the regulation of G-quadruplex formation and the functional consequ”