Exploring Sequence Space to Design Controllable G-Quadruplex Topology Switches

Abstract

As non-classical nucleic acid structures, G-quadruplexes (G4s) not only play important roles in gene regulation and stability maintenance, but are also widely used in nanotechnology. Structural diversity is one of the main factors explaining the popularity of G-quadruplexes, but a comprehensive and integrated study of different factors determining G4 structural versatility is currently lacking. Herein, starting from a common G4 sequence, (G 3 T) 3 G 3 , as the parent chain, and then taking advantage of G4 versatility, we present a variety of strategies to control G4 structure, based on the regulation of loop length and flanking sequences, cation (type and concentration), and molecular crowding. These strategies allow to convert the G4 topology from parallel to hybrid, antiparallel, and then back to parallel. Such structural diversity reveals the coding regulation ability of G4 structures, with potential applications in nanotechnology.

Opportunities and challenges for DNA in atomic and close-to-atomic scale manufacturing

“…A series of DNA-metal complexes have been proved to be powerful tools for the treatment of disease and diagnosis [62,65]. The specific binding of hemin to G-quadruplex DNA (G4) has been widely investigated, which is a typical example of metal complexes selectively binding to DNA structures [66]. G4 is a structure consisting of four guanine bases bound together in a Hoogsteen fashion [67].…”

Engineering fluorescent protein chromophores with an internal reference for high-fidelity ratiometric G4 imaging in living cells

“…G-quadruplexes (G4s) are noncanonical nucleic acid secondary structures formed by guanine-rich sequences and contain two or more stacked G-quartets, which are stabilized by Hoogsteen hydrogen bonding. [1][2][3][4][5] G4s play significant roles in multiple biological processes, such as the DNA replication regulation, 6,7 gene expression and stability, [8][9][10] and telomere biology. 11,12 Thus, developing a high-fidelity and reliable G4s visualization approach is highly significant.…”

Parallel G-quadruplex folds via multiple paths involving G-tract stacking and structuring from coil ensemble

“…In contrast, for antiparallel G-strands two guanines in a given quartet have opposite glycosidic orientations (Figure 1) (10). Additionally, a single-nucleotide loop predominantly folds into a propeller topology and thus only supports a parallel G-strand orientation (11)(12)(13).…”