Duplex-tetraplex equilibria in guanine- and cytosine-rich DNA

Noncanonical four-stranded DNA structures, including G-quadruplexes and i-motifs, have been discovered in the cell and are implicated in a variety of genomic regulatory functions. The tendency of a specific guanine- and cytosine-rich region of genomic DNA to adopt a four-stranded conformation depends on its ability to overcome the constraints of duplex base-pairing by undergoing consecutive duplex-to-coil and coil-to-tetraplex transitions. The latter ability is determined by the balance between the free energies of participating ordered and disordered structures. In this review, we present an overview of the literature on the stability of G-quadruplex and i-motif structures and discuss the extent of duplex-tetraplex competition as a function of the sequence context of the DNA and environmental conditions including temperature, pH, salt, molecular crowding, and the presence of G-quadruplex-binding ligands. We outline how the results of in vitro studies can be expanded to understanding duplex-tetraplex equilibria in vivo.