A four-stranded DNA or RNA structure formed by stacked guanine tetrads, often in gene promoters.A G-quadruplex is a folded structure that DNA or RNA can adopt in regions rich in the base guanine. Instead of the familiar double helix, four guanine bases arrange themselves in a flat square, called a tetrad, held together by hydrogen bonds. Several such squares stack on top of one another, and the whole assembly is stabilised by a central ion, usually potassium. These structures form most readily in single-stranded regions, such as the ends of chromosomes or the regulatory regions near the start of genes. They matter because they can block or modulate the machinery that copies DNA and reads genes, so they are thought to act as molecular switches. Their presence in gene promoters and at chromosome ends has made them a target of interest in cancer research and in the design of drugs that lock them in place.
A run of guanines in a single strand can fold back on itself so that four guanines come together in a planar arrangement, each pairing with two neighbours through hydrogen bonds. Stacking several tetrads produces a stable, compact structure with a central channel. A positively charged ion, typically potassium, sits in that channel and coordinates the oxygen atoms of the guanines, greatly increasing stability. The exact shape depends on the sequence and on which ions are available.
G-quadruplexes are studied as drug targets in oncology, and their formation is exploited in biosensors and in some DNA-based nanotechnologies.
The ends of human chromosomes, the telomeres, are rich in guanine and can fold into G-quadruplexes; stabilising these structures with small molecules can interfere with the enzyme that extends telomeres in cancer cells.