G-quadruplexes, four-stranded structures formed by Guanine-rich nucleic acids, are implicated in many physiological and pathological processes. G-quadruplex-forming sequences are abundant in genomic DNA, and G-quadruplexes have recently been shown to exist in the genome of mammalian cells. However, how G-quadruplexes are formed in the genomes remains largely unclear. Here, we show that G-quadru...

The G-quadruplexes are four-stranded nucleic acid structures with guanine-rich sequences that play important biological roles in, for example, regulating telomerase association and activity. Recent evidence supports the hypothesis that the telomeric G-quadruplex DNA represents a target of novel anticancer drug medication. In this work, we present results of the molecular electrostatic potential...

Due to the long-range nature of high-order interactions between distal components in a biomolecule, transition dynamics of tertiary structures is often too complex to profile using conventional methods. Inspired by the exploded view in mechanical drawing, here, we used laser tweezers to mechanically dissect high-order DNA structures into two constituting G-quadruplexes in the promoter of the hu...

The arrangement of the human telomeric quadruplex in physiologically relevant conditions has not yet been unambiguously determined. Our spectroscopic results suggest that the core quadruplex sequence G(3)(TTAG(3))(3) forms an antiparallel quadruplex of the same basket type in solution containing either K(+) or Na(+) ions. Analogous sequences extended by flanking nucleotides form a mixture of th...

Previous studies have demonstrated that nuclease hypersensitivity regions of several proto-oncogenic DNA promoters, situated upstream of transcription start sites, contain guanine-rich tracts that form intramolecular G-quadruplexes stabilized by stacked G•G•G•G tetrads in monovalent cation solution. The human c-kit oncogenic promoter, an important target in the treatment of gastrointestinal tum...

A label-free fluorescence K(+) assay was developed using riboflavin, a new G-quadruplex ligand, and a G-quadruplex sequence (PW17).

G-quadruplexes have shown great promise as chemotherapeutic targets, probably by inhibiting telomere elongation or downregulating oncogene expression. There have been many G-quadruplex ligands developed over the years but only a few have drug-like properties. Consequently only a few G-quadruplex ligands have entered clinical trials as cancer chemotherapeutic agents. The DNA minor groove ligand,...

The promoter of the human KRAS proto-oncogene contains a structurally polymorphic nuclease hypersensitive element (NHE) whose purine strand forms a parallel G-quadruplex structure (called 32R). In a previous work we reported that quadruplex 32R is recognized by three nuclear proteins: PARP-1, Ku70 and hnRNP A1. In this study we describe the interaction of recombinant hnRNP A1 (A1) and its deriv...

G-quadruplexes are tetraplex structures of nucleic acids that can form in G-rich sequences. Their presence and functional role have been established in telomeres, oncogene promoters and coding regions of the human chromosome. In particular, they have been proposed to be directly involved in gene regulation at the level of transcription. Because the HIV-1 Nef protein is a fundamental factor for ...

The G-rich strand of human telomeric DNA can fold into a four-stranded structure called G-quadruplex and inhibit telomerase activity that is expressed in 85-90% tumor cells. For this reason, telomere quadruplex is emerging as a potential therapeutic target for cancer. Information on the structure of the quadruplex in the physiological environment is important for structure-based drug design tar...