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

Chemistry. 2021 Jun 16;27(34):8865-8874. doi: 10.1002/chem.202100993. Epub 2021 May 13.

Abstract

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.

Keywords: Guanine quadruplexes; electronic circular dichroism; immunofluorescence; molecular dynamics; oxidative DNA lesions.

MeSH terms

  • Circular Dichroism
  • DNA / metabolism
  • G-Quadruplexes*
  • Humans
  • Nucleic Acid Conformation
  • Oxidative Stress
  • Telomerase* / metabolism
  • Telomere / metabolism

Substances

  • DNA
  • Telomerase