Advancement in the Structural Polymorphism of G-Quadruplexes

Abstract

Genomes contain a large number of putative guanine-rich sequences, specifically on promoter regions, untranslated regions (UTR’s) and telomeres etc. that could form guanine-quadruplexes, and may serve as important structural and regulatory elements. They can also be the source of genomic instability which may lead to cancer, aging and human genetic diseases. Four guanines in the same plane, joined together with Hoogsteen hydrogen bonding, and stacked over one another resulting in guanine tetrads, give rise to an incredible class of G-quadruplexes. An extensive range of G-quadruplex structures is well documented, where they differ in number of strands (uni, bi, or tetramolecular), conformations (parallel, antiparallel or mixed), shapes (chair or basket form), or types of loops (edgewise/ lateral, diagonal, double chain reversal/ propeller, or V-shaped loops) etc. With advancements in the techniques, various new multistranded G-rich DNA structures are enriching the DNA structural databases. The most recent ones are (3+1) G-quadruplex, Tri-G-quadruplex, G-triplex DNA etc. which actually add to the diversity of G-quadruplex structures. Exploring their polymorphism with various biophysical and biochemical techniques has hence become extremely important. This review mainly focuses on the discussion of these unusual and comparatively new polymorphic G-quadruplex DNA structures. The robustness of these unique (3+1) G-quadruplex or G-triplex or tri-G-quadruplex structures actually can be exploited for providing a strong foundation for the designing of structure-specific drugs. Recently, G-quadruplex structures have been quantitatively visualized in human cells by engineering structure-specific antibody. Considering these developments, the mapping of G-quadruplex structures in genome may now be possible, with a goal of controlling the gene functions or other cellular processes, which might be involved in diseases like cancer.