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1 Introduction
Genetic information is stored in the cellular DNA of every living organism [1]. However, this crucial macromolecule is continuously exposed to the oxidative stresses, which can lead to various types of damage. Until now, more than 80 DNA lesions have been identified [2-4]. One of the main sources of their formation is the activity of reactive oxygen species (ROS). These molecules may be generated by endocellular processes such as mitochondria-catalyzed electron transport reactions, metal catalysed reactions, during inflammation by neutrophils and macrophages, and/or physical external factors such as ionisation radiation [5]. It is important to mention that ionisation radiation (alpha, heavy ions, beta, gamma, X-ray, UV) can cause damage to DNA both directly and indirectly, depending on the source and energy. Such damage includes a single/double-strand break, nucleobase damage, and hydrogen atom abstraction from nucleobase moiety [3]. Among all ROS, the hydroxyl radical (•OH) has been found to be the most harmful one (for example, in cell-produced reactions, via the Haber-Weiss reaction), while the hydrogen peroxide (H2O2) and superoxide radical (O2•–) can be recognized as low-active species [5]. In a cell, O2•– formed as a by-product of respiratory cycles, is rapidly converted into oxygen and H2O2 by a superoxide dismutase (SOD) or in a self-dismutation process [6]. Subsequently, catalase converts hydrogen peroxide to a “safe” water molecule [2]. On the other hand, once ds-DNA has been one-electron oxidized by a variety of photo-oxidants, i.e. antraquinone, the generated radical cation hole can hop reversibly through the double-helix until it is trapped, usually by the reaction with H2O of the formed guanine radical cation (G•+) [7], Fig. 1. Alternatively, a generated G•+ can be rearranged by a proton loss to a neutral radical, which can react with O2•– [8,9]. The one-electron oxidation process, described above, is discussed further in the Results section of this article. As a result of this, two reaction paths are possible: either one with a water molecule addition, or one without [10,11]. The first path leads to an 8-oxo-7,8-dihydroguanine (8-oxoG) formation, while the second finally leads to a 2,2,4-triamino-5(2H)-oxazolone. The mechanisms of the these reactions are presented in Fig. 2 [9]. It is worth pointing out that of all the nucleobases, 2′-deoxyguanosine possesses the lowest ionisation potential [7]. Moreover, in an oxidative condition, guanine can be converted to other “lesions”, such as dehydro-guanidinohydantoin, oxaluric acid, spiroiminohydantoin, etc. [11,13]. Most of the generated DNA lesions are removed from the genome by a “cell defence machinery”, i.e. a base or nucleotide repair system (BER, NER) [12-15]. However, the first forces against ROS/ radicals in cells comprise of antioxidants and enzymes [16]. These relatively small molecules protect the cell against toxic species formation. Therefore, the discovery by Wang et al. in 2007 that a phosphorothiate (PT) internucleotide bond can naturally appear in the bacterial DNA [17] raises the question of whether their role in the genome is protective or not. This problem is supported by the observation that spermine disulphide can protect ds-DNA from the one-electron oxidative/charge migration process that can lead to its damage [18]. In 2013, the one-electron oxidation of DNA containing the PT moiety was investigated for the first time by Sevilla et al. [19]. In their work, the authors postulated that the backbone-to-base hole-transfer mechanism was induced by the Cl2•–. However, due to the nature of the chlorine anion radical, the authors did not consider the influence of PT on the long charge migration process through ds-DNA, induced by photosensitizers (e.g. antraquinone). Therefore, in this work, the influence of the phosphorothioate internucelotide bond on the light-induced oxidation/charge migration process was investigated using the Schuster strategy in which the antraquinone moiety was covalently linked to one strand of ds- DNA [20].
Graphical representation of long-distance oxidation of ds-DNA process. (PhotoS – photosensitizer, e.g.: anthraquinone, B-nucleobase, G-guanine, SOD-superoxide dismutase, Cat-catalase, Self-D – self-dismutation process).
The formation of 8-oxoG and oxazolone in the one-electron oxidation process (8,9).
