Nucleolin–G-quadruplex DNA complex

The **nucleolin–G-quadruplex DNA complex** refers to a molecular entity formed when the nucleic acid-binding protein nucleolin binds to G-quadruplex secondary structures present in guanine-rich regions of DNA—especially in the promoters of certain genes, such as c-MYC. **Nucleolin** is a multifunctional, predominantly nucleolar protein with roles in ribosome biogenesis, cell proliferation, and apoptosis[1][2][3]. It specifically recognizes and binds parallel G-quadruplex DNA with high affinity, inducing or stabilizing the structure through its RNA recognition motifs (RRMs) and RGG-rich domains[1][4]. Formation of the nucleolin–G-quadruplex complex in promoters such as c-MYC results in transcriptional repression and is implicated in epigenetic regulation of gene expression[4][6]. The interaction is functionally important in cancer biology, where G-quadruplex stabilization suppresses oncogene transcription, and in viral biology, where G-quadruplexes in retroviral promoters reduce viral transcription[5]. Small molecules that target this complex are under investigation as anticancer or antiviral therapeutics, with Quarfloxin (CX-3543) being a clinical-stage example disrupting nucleolin–G-quadruplex interaction[4][5]. The target is considered pharmacologically tractable, but concerns remain about global transcriptomic effects, toxicity, and off-target actions if global G-quadruplex stabilization occurs.

Other names

Nucleolin–G4 DNA complexNucleolin–G-quadruplex complexNCL–G4 DNA complex

Stabilization of G-quadruplex structures in gene promoters (e.g., c-MYC), resulting in transcriptional repression. Disruption of protein–G-quadruplex interaction inhibits regulatory complexes, which can modulate oncogene expression.