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Forever Young: Structural Stability of Telomeric Guanine Quadruplexes in the Presence of Oxidative DNA Lesions **
Author(s) -
Miclot Tom,
Corbier Camille,
Terenzi Alessio,
Hog Cécilia,
Grandemange Stéphanie,
Barone Giampaolo,
Monari Antonio
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202100993
Subject(s) - telomere , circular dichroism , oxidative stress , telomerase , guanine , dna , g quadruplex , oxidative phosphorylation , chemistry , biophysics , microbiology and biotechnology , biochemistry , biology , gene , nucleotide
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.