Absorption of Low-Energy UV Radiation by Human Telomere G-Quadruplexes Generates Long-Lived Guanine Radical Cations.
(2017) Journal of the American chemical society — Vol. 139, n° 30, p. 10561-10568 (2017)
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- Authors
Markovitsi, Dimitra 
- Abstract
- Telomeres, which are involved in cell division, carcinogenesis, and aging and constitute important therapeutic targets, are prone to oxidative damage. This propensity has been correlated with the presence of guanine-rich sequences, capable of forming four-stranded DNA structures (G-quadruplexes). Here, we present the first study on oxidative damage of human telomere G-quadruplexes without mediation of external molecules. Our investigation has been performed for G-quadruplexes formed by folding of GGG(TTAGGG) single strands in buffered solutions containing Na cations (TEL21/Na). Associating nanosecond time-resolved spectroscopy and quantum mechanical calculations (TD-DFT), it focuses on the primary species, ejected electrons and guanine radicals, generated upon absorption of UV radiation directly by TEL21/Na. We show that, at 266 nm, corresponding to an energy significantly lower than the guanine ionization potential, the one-photon ionization quantum yield is 4.5 × 10. This value is comparable to that of cyclobutane thymine dimers (the major UV-induced lesions) in genomic DNA; the quantum yield of these dimers in TEL21/Na is found to be (1.1 ± 0.1) × 10. The fate of guanine radicals, generated in equivalent concentration with that of ejected electrons, is followed over 5 orders of magnitude of time. Such a quantitative approach reveals that an important part of radical cation population survives up to a few milliseconds, whereas radical cations produced by chemical oxidants in various DNA systems are known to deprotonate, at most, within a few microseconds. Under the same experimental conditions, neither one-photon ionization nor long-lived radical cations are detected for the telomere repeat TTAGGG in single-stranded configuration, showing that secondary structure plays a key role in these processes. Finally, two types of deprotonated radicals are identified: on the one hand, (G-H) radicals, stable at early times, and on the other hand, (G-H) radicals, appearing within a few milliseconds and decaying with a time constant of ∼50 ms.
- Affiliations
CEA DICO
Citations
Banyasz, A., Martínez-Fernández, L., Balty, C., Perron, M., Douki, T., Improta, R., & Markovitsi, D. (2017). Absorption of Low-Energy UV Radiation by Human Telomere G-Quadruplexes Generates Long-Lived Guanine Radical Cations. Journal of the American chemical society, 139(30), 10561-10568. https://doi.org/10.1021/jacs.7b05931 (Original work published 2017)