Analysis of Guanine Oxidation Products in Double-Stranded DNA and Proposed Guanine Oxidation Pathways in Single-Stranded, Double-Stranded or Quadruplex DNA

Abstract

Guanine is the most easily oxidized among the four DNA bases, and some guanine-rich sequences can form quadruplex structures. In a previous study using 6-mer DNA d(TGGGGT), which is the shortest oligomer capable of forming quadruplex structures, we demonstrated that guanine oxidation products of quadruplex DNA differ from those of single-stranded DNA. Therefore, the hotooxidation products of double-stranded DNA (dsDNA) may also differ from that of quadruplex or single-stranded DNA, with the difference likely explaining the influence of DNA structures on guanine oxidation pathways. In this study, the guanine oxidation products of the dsDNA d(TGGGGT)/d(ACCCCA) were analyzed using HPLC and electrospray ionization-mass spectrometry (ESI-MS). As a result, the oxidation products in this dsDNA were identified as 2,5-diamino-4H-imidazol-4-one (Iz), 8-oxo-7,8-dihydroguanine (8oxoG), dehydroguanidinohydantoin (Ghox), and guanidinohydantoin (Gh). The major oxidation products in dsDNA were consistent with a combination of each major oxidation product observed in single-stranded and quadruplex DNA. We previously reported that the kinds of the oxidation products in single-stranded or quadruplex DNA depend on the ease of deprotonation of the guanine radical cation (G•+) at the N1 proton. Similarly, this mechanism was also involved in dsDNA. Deprotonation in dsDNA is easier than in quadruplex DNA and more difficult in single-stranded DNA, which can explain the formation of the four oxidation products in dsDNA.

Gas-Phase Oxidation via Ion/Ion Reactions: Pathways and Applications

“…This is almost identical to the control spectrum except for the addition of oxygen to the w 5 ion and the lack of the w 4 ion. Furthermore, guanine is the most readily oxidized nucleobase in condensed-phase experiments [73,74], supporting the observations from this gas-phase oxidation experiment. This is the first demonstration of the oxidation of DNA via ion/ion reactions.…”

Analytics of oxidative stress markers in the early diagnosis of oxygen DNA damage

“…In the first stage of the process an electron from a molecule of guanine is abstracted with the participation of a hydroxyl radical (the abstraction of an electron can also be an effect of quantum radiation or some other equally strong attack, by an oxidant such as a ferrous radical 15 , or as a result of the reaction of type I photosensitizers). [16][17][18][19] In the second stage of the reaction, the final product is formed (Fig. 4).…”

Radioresistance of GGG sequences to prompt strand break formation from direct-type radiation damage

“…It has been established that guanine is the most effective sink for oxidative damage in DNA (Steenken and Jovanovic 1997; Morikawa et al 2014). As such, we focused on the cleavage probabilities at isolated guanine bases and guanine triplet repeats within two double-stranded sequences of interest, designated single-G and triple-G (Table 1) annealed to their complements, respectively.…”

“…As free base release analysis, quantification of products like C (8-oxo-G), and the ESR studies of mechanisms of 8-oxo-G cation radical formation from guanine cation radical has pointed to guanine as a sink for DNA damage induced by an oxidative pathway (Shukla et al 2004; Steenken and Jovanovic 1997; Morikawa et al 2014) we analyzed the relative probability of strand break occurrence at a guanine triplet compared to a single guanine base with identical flanking bases. This investigation builds on previous work in which ultraviolet A (UVA, wavelength 400-315 nanometers) irradiation studies identified GGG as a sink for base damage, showing dramatic increases in the production of 8-oxo-G through one-electron oxidation of the G within GGG regions, which resulted in strand breaks after hot piperidine treatment (Chung et al 1992).…”