Discovery of “folded DNA” structures in human cells: Potential drug targets

Abstract

What is known and objective: The double-helical conformation of human DNA (hDNA) is so axiomatic that it is called the “canonical” form. Recently, though, intrastrand folds (“I-motifs” and “G-quadruplexes”) have been identified in hDNA. These could be targets for novel drug discovery. Comment: Any interruption of the canonical form of hDNA fundamentally impacts the normal progression of transduction and translation. In particular, the synthesis of receptors and cognate protein ligands would be affected, as well as their affinity for—and signal transduction of—pharmacotherapeutic agents. Recent studies have identified normally occurring, folded structures superimposed on the usual double-helix motif of hDNA. What is new and conclusion: The newly identified “folded DNA” structures (“I-motifs” and “G-quadruplexes”) could represent novel drug-discovery targets, most likely for cancer.