Quantitative visualization of DNA G-quadruplex structures in human cells.
Nature Chemistry 2013, Jan 20
Giulia Bifﬁ, David Tannahill, John McCafferty and Shankar Balasubramanian.
Department of Biochemistry, University of Cambridge
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.