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Absorption of Low-Energy UV Radiation by Human Telomere G‑Quadruplexes Generates Long-Lived Guanine Radical Cations
journal contribution
posted on 2017-07-24, 15:39 authored by Akos Banyasz, Lara Martínez-Fernández, Clémence Balty, Marion Perron, Thierry Douki, Roberto Improta, Dimitra MarkovitsiTelomeres, 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)3 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 × 10–3. 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)
× 10–3. 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-H2)• radicals, stable at early times,
and on the other hand, (G-H1)• radicals,
appearing within a few milliseconds and decaying with a time constant
of ∼50 ms.