Guanine-rich DNA sequences (G-rich DNA)

Guanine-rich DNA sequences are genomic regions characterized by a high density of guanine nucleotides, which are capable of folding into non-canonical four-stranded structures known as G-quadruplexes (G4s). These sequences are non-randomly distributed throughout the human genome, clustering in functional regions such as telomeres, ribosomal DNA, and the promoter regions of potent oncogenes like MYC, BCL2, and KRAS (Rhodes & Lipps, 2015, Nucleic Acids Res). Biologically, these structures act as regulatory elements that influence DNA replication, gene transcription, and telomere protection. In the context of disease, G-rich regions are frequently associated with cancer progression and neurodegenerative disorders, such as C9orf72-linked amyotrophic lateral sclerosis, where repeat expansions form toxic structures (DeJesus-Hernandez et al., 2011, Neuron). Therapeutic intervention typically involves small molecules that stabilize G-quadruplexes to inhibit oncogene expression or traditional alkylating agents like cisplatin that bind guanine to cause lethal DNA damage (Dasari & Bernard Tchounwou, 2014, Eur J Pharmacol). However, targeting these sites presents significant challenges regarding selectivity and the risk of systemic genotoxicity.

Other names

G-quadruplexG4 DNAG-rich regionsGuanine-rich DNATelomeric DNA

Drugs targeting these regions typically act by stabilizing non-canonical structures like G-quadruplexes to inhibit transcription and replication, or by forming covalent adducts and cross-links with guanine bases to induce DNA damage and apoptosis (Dasari & Bernard Tchounwou, 2014; Rhodes & Lipps, 2015).