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Quantitative visualization of DNA G-quadruplex structures in human cells

Nature Chemistry volume 5, pages 182186 (2013) | Download Citation

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.

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Acknowledgements

We thank T. Pope for his kind help with the phage display, W. Reik, R. Rodriguez and D. Sanders for stimulating discussions and Cancer Research UK for funding.

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Affiliations

  1. Cancer Research UK, Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK

    • Giulia Biffi
    • , David Tannahill
    •  & Shankar Balasubramanian
  2. Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK

    • John McCafferty
  3. Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK

    • Shankar Balasubramanian

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Contributions

G.B. carried out the experiments, J.M. advised on the phage display and G.B., D.T. and S.B. designed the experiments. G.B., D.T. and S.B. co-wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Shankar Balasubramanian.

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DOI

https://doi.org/10.1038/nchem.1548

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