Parallel G-quadruplex DNA (G4 DNA) (G4 DNA)

Parallel G-quadruplex DNA (G4 DNA) is a non-canonical nucleic acid structure formed by guanine-rich sequences where four strands align in a parallel orientation, stabilized by stacked G-tetrads and monovalent cations (Rhodes & Lipps, 2015, Nucleic Acids Research). These structures are predominantly located in critical genomic regions, including the promoters of oncogenes like c-MYC and KRAS, as well as at telomeric ends (Huppert & Balasubramanian, 2007, Nucleic Acids Research). Biologically, parallel G4s serve as regulatory elements that modulate gene transcription, DNA replication, and telomere protection by acting as physical barriers or recruitment sites for proteins. In disease states, particularly cancer, the formation and stability of these structures are often dysregulated, contributing to the overexpression of growth-promoting genes. Therapeutic strategies involve using small-molecule ligands to stabilize parallel G4s, which can selectively repress oncogene expression or disrupt telomere maintenance, leading to cell cycle arrest and apoptosis in malignant cells (Balasubramanian et al., 2011, Nature Reviews Drug Discovery). Consequently, parallel G-quadruplex DNA represents a high-value target for precision oncology and the development of novel chemotherapeutic agents.

Other names

Parallel G4 DNAG-quadruplex DNAG4-DNAG-tetraplex DNA

Small-molecule ligands bind to and stabilize the G-tetrad stacks of the parallel G-quadruplex, which physically blocks the progression of RNA polymerase or DNA polymerase, inhibits telomerase access to telomeres, and triggers a DNA damage response (Balasubramanian et al., 2011, Nature Reviews Drug Discovery; Drygin et al., 2011, Cancer Research).