G-quadruplex DNA structure at G4-duplex junction (G4-duplex junction)

G-quadruplex (G4) DNA structures are non-canonical, four-stranded secondary structures formed in guanine-rich sequences through Hoogsteen hydrogen bonding (MDPI, 2021; NIH, 2023). These structures are highly prevalent in the promoter regions of key oncogenes such as MYC, BCL2, and KRAS, where they often exist at the junction between the G4 motif and the flanking duplex DNA (MDPI, 2017; NIH, 2021). The G4-duplex junction represents a unique structural interface that can be specifically targeted by small molecules to modulate gene expression (NIH, 2021). Stabilization of these structures typically acts as a transcriptional repressor, preventing the binding of transcription factors or the progression of RNA polymerase, thereby downregulating oncogene expression (IntechOpen, 2013; MDPI, 2017). Beyond transcription, G4 structures at these junctions are involved in DNA replication and genome stability, making them attractive targets for cancer therapy (NIH, 2013; NIH, 2021). Drugs like CX-5461 and various G4 ligands aim to stabilize these structures to induce replication stress and apoptosis in cancer cells, often exploiting synthetic lethal relationships in DNA repair-deficient tumors (PNAS, 2012; NIH, 2021).

Other names

G-quadruplexG4G4-duplex hybridPromoter G-quadruplexNon-canonical DNA structureTetraplex DNAG-quadruplex-duplex interface

Stabilization of G-quadruplex structures at promoter regions to inhibit oncogene transcription, induction of replication stress, and inhibition of telomerase activity (NIH, 2023; MDPI, 2017).