Journal
CHEMISTRY-A EUROPEAN JOURNAL
Volume 27, Issue 34, Pages 8865-8874Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.202100993
Keywords
electronic circular dichroism; Guanine quadruplexes; immunofluorescence; molecular dynamics; oxidative DNA lesions
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Funding
- Ministero dell'Universita e Ricerca Scientifica e Tecnologica, Italy
- Universita di Palermo, Italy
- Universite de Lorraine, France
- CNRS, France
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This study demonstrated the crucial role of the stability of G-quadruplex in telomeric DNA in resisting oxidative stress and as an inhibitor of telomerase, an enzyme overexpressed in most cancers associated with oxidative stress. The combined experimental and computational investigation utilized circular dichroism, cellular immunofluorescence assays, and molecular dynamics simulations to identify these roles.
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.
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