Forever young: Structural stability of telomeric guanine quadruplexes in the presence of oxidative DNA lesions

Tom Miclot (1, 2) , Camille Corbier (3) , Alessio Terenzi (1) , Cécilia Hognon (2) , Stéphanie Grandemange (3) , Giampaolo Barone (1) , Antonio Monari (2)

1 Università degli studi di Palermo - University of Palermo
2 LPCT - Laboratoire de Physique et Chimie Théoriques
3 CRAN - Centre de Recherche en Automatique de Nancy

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.

Mots clés: Guanine quadruplexes; electronic circular dichroism; immunofluorescence; molecular dynamics; oxidative DNA lesions

Domaines: Automatique / Robotique

Tom Miclot, Camille Corbier, Alessio Terenzi, Cécilia Hognon, Stéphanie Grandemange, et al.. Forever young: Structural stability of telomeric guanine quadruplexes in the presence of oxidative DNA lesions. Chemistry - A European Journal, 2021, 27 (34), pp.8865-8874. ⟨10.1002/chem.202100993⟩. ⟨hal-03503711⟩