Forever Young: Structural Stability of Telomeric Guanine Quadruplexes in the Presence of Oxidative DNA Lesions

Human telomeric DNA, in G‐quadruplex (G4) conformation, is characterized by a remarkable structural stability that confers it the capacity to resist to oxidative stress producing one or even clustered 8‐oxoguanine (8oxoG) lesions. We present a combined experimental/computational investigation, by using circular dichroism in aqueous solutions, cellular immunofluorescence assays and molecular dynamics simulations, that identifies the crucial role of the stability of G4s to oxidative lesions, related also to their biological role as inhibitors of telomerase, an enzyme overexpressed in most cancers associated to oxidative stress. The structural stability of guanine quadruplexes in the presence of oxidative lesions is revealed using molecular dynamics simulations, CD spectroscopy and immunofluorescence.