6533b81ffe1ef96bd12784c4

RESEARCH PRODUCT

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

Antonio MonariCécilia HognonStéphanie GrandemangeCamille CorbierTom MiclotGiampaolo BaroneAlessio Terenzi

subject

chemistry.chemical_classificationTelomeraseCircular dichroismmedicine.diagnostic_testOxidative phosphorylationImmunofluorescencemedicine.disease_causeMolecular dynamicschemistry.chemical_compoundEnzymechemistrymedicineBiophysicsDNAOxidative stress

description

AbstractHuman telomeric DNA (h-Telo), 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 lesions. We present a combined experimental/computational investigation, by using circular dichroism in aqueous solutions, cellular immunofluorescence assays and molecular dynamics (MD) 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.

https://doi.org/10.1101/2020.11.26.399741