DNA G-Quadruplex and i-Motif Structure Formation Is Interdependent in Human Cells
Jessica J. King, Kelly L. Irving, Cameron W. Evans, Rupesh V. Chikhale, Rouven Becker, Christopher J. Morris, Cristian David Peña Martinez, Peter Schofield, Daniel Christ, Laurence H. Hurley, Zoë A. E. Waller, K. Swaminathan Iyer, Nicole M. Smith
Abstract
Guanine- and cytosine-rich nucleic acid sequences have the potential to form secondary structures such as G-quadruplexes and i-motifs, respectively. We show that stabilization of G-quadruplexes using small molecules destabilizes the i-motifs, and vice versa, indicating these gene regulatory controllers are interdependent in human cells. This has important implications as these structures are predominately considered as isolated structural targets for therapy, but their interdependency highlights the interplay of both structures as an important gene regulatory switch.