The Unusual DNA Structures Driving Cancer: What Are G-Quadruplexes?

DNA is best known for its iconic double-helix structure, but it can also fold into alternative shapes known as G-quadruplexes (G4s). These unusual DNA and RNA structures are increasingly recognized as important regulators of gene expression, genome stability, and cancer biology.

Can naturally occurring G-quadruplexes (G4s) in the genome be used as molecular anchor points to selectively degrade proteins associated with G4-rich chromatin? This was the question addressed by Shankar Balasubramanian and colleagues in a landmark 2026 study published in Nature Chemistry. Rather than targeting G4 structures directly, the researchers asked whether G4s could serve as docking sites that guide the cell's protein degradation machinery to specific chromatin-associated proteins.

Our immune system faces a tricky balancing act every day. It needs to stay quiet enough to avoid attacking your own tissues, yet be ready to spring into action the moment a virus shows up. 

A new study published in Science Advances reveals that an RNA-unwinding protein called DHX36 sits at the heart of this balancing act, serving as a molecular dimmer switch for antiviral immunity. 

Millions of people worldwide live with metabolic syndrome; the cluster of conditions including obesity, high blood sugar, and insulin resistance that raises the risk of diabetes, fatty liver disease, and, less obviously, cancer. Scientists have long known the statistical link between metabolic disease and cancer, but the molecular "why" has remained frustratingly unclear. A new study from the University of Salzburg may have cracked open an important piece of that puzzle, and it involves some unusual structures in your DNA.

Small molecules that bind RNA offer promising therapeutic strategies, particularly for diseases such as cancer, where gene expression is difficult to regulate with conventional protein-targeting drugs. Many of these RNA structures are sensitive to their surrounding sequence. A single-nucleotide variant (SNV), such as a cancer-associated somatic mutation, can dramatically reshape an RNA molecule's three-dimensional structure and either enhance or abolish drug binding. 

 For years, G-quadruplexes have dominated discussions of noncanonical DNA biology. This study, led by researchers at University College London, along with collaborators at the John Innes Centre, the University of Sheffield, and the Beckman Research Institute of the City of Hope, suggests that the story is more nuanced.  i-motif could be another important regulatory player.  Rather than asking whether a G-quadruplex or an i-motif controls a gene, researchers may need to consider how both structures cooperate in gene expression.