Peroxy Radical Oxidation of Thymidine

Martini, Michela; Termini, John

doi:10.1021/tx960154l

Cited by 49 publications

(37 citation statements)

References 57 publications

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“…Significantly, peroxyl radicals are reported to abstract hydrogen atoms from thymine bases and from deoxyribose to form ROOH moieties. 37,38 Such damage sites would serve as plausible sources for OH − desorption under electron impact. Moreover, since it has been observed that radiation-induced radicals in DNA and related molecules, that form and trap at cryogenic temperatures, can combine upon heating, 39 it is interesting to speculate that the decrease in O − signal and increase in OH − desorption observed with increasing film temperature in Fig.…”

Section: Resultsmentioning

confidence: 99%

Low energy electron stimulated desorption from DNA films dosed with oxygen

Mirsaleh-Kohan

Bass

Cloutier

et al. 2012

The Journal of Chemical Physics

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Desorption of anions stimulated by 1-18 eV electron impact on self-assembled monolayer (SAM) films of single DNA strands is measured as a function of film temperature (50-250 K). The SAMs, composed of 10 nucleotides, are dosed with O 2 . The OH − desorption yields increase markedly with exposure to O 2 at 50 K and are further enhanced upon heating. In contrast, the desorption yields of O − , attributable to dissociative electron attachment to trapped O 2 molecules decrease with heating. Irradiation of the DNA films prior to the deposition of O 2 shows that this surprising increase in OH − desorption, at elevated temperatures, arises from the reaction of O 2 with damaged DNA sites. These results thus appear to be a manifestation of the so-called "oxygen fixation" effect, well known in radiobiology.

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Section: Resultsmentioning

confidence: 99%

Low energy electron stimulated desorption from DNA films dosed with oxygen

Mirsaleh-Kohan

Bass

Cloutier

et al. 2012

The Journal of Chemical Physics

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“…In particular, H 2 O 2 is a potential source for hydroxyl radical (·OH), one of the most dangerous radicals formed through the Fenton reaction in the presence of transition metal ions, as iron. Additionally, azo-initiators like AAPH induce the formation of peroxyl radicals, capable of initiating the chain reaction of lipid peroxidation (Cao et al, 1997;Martini & Termini 1997;Kanno et al, 2003).…”

Section: Antioxidant Activitymentioning

confidence: 99%

Hepatoprotective effects and HSV-1 activity of the hydroethanolic extract ofCecropia glaziovii(embaúba-vermelha) against acyclovir-resistant strain

Petronilho¹,

Costa²,

Kappel³

et al. 2012

Pharmaceutical Biology

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“…4B). DISCUSSION fU is one of the major oxidative thymine lesions found in DNA and nucleoside that were exposed to ionizing radiation (44 -46), Fenton-type reactions (46,47), photosensitized reactions (48,49), and peroxy radicals (50). The yield of fU in Fenton-type reactions and ␥-irradiation is comparable to those of 8-oxoG (47) and 5-hydroxypyrimidines (45) that are known as major mutagenic oxidative base lesions (51)(52)(53)(54)(55).…”

Section: Fig 1 Hplc Analysis Of Nucleosides In 25fmentioning

confidence: 98%

Oxidation of Thymine to 5-Formyluracil in DNA Promotes Misincorporation of dGMP and Subsequent Elongation of a Mismatched Primer Terminus by DNA Polymerase

Masaoka

Terato

Kobayashi

et al. 2001

Journal of Biological Chemistry

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5-Formyluracil (fU) is a major oxidative thymine lesion generated by ionizing radiation and reactive oxygen species. In the present study, we have assessed the influence of fU on DNA replication to elucidate its genotoxic potential. Oligonucleotide templates containing fU at defined sites were replicated in vitro by Escherichia coli DNA polymerase I Klenow fragment deficient in 3-5-exonuclease. Gel electrophoretic analysis of the reaction products showed that fU constituted very weak replication blocks to DNA synthesis, suggesting a weak to negligible cytotoxic effect of this lesion. However, primer extension assays with a single dNTP revealed that fU directed incorporation of not only correct dAMP but also incorrect dGMP, although much less efficiently. No incorporation of dCMP and dTMP was observed. When fU was substituted for T in templates, the incorporation efficiency of dAMP (f A ‫؍‬ V max /K m ) decreased to 1 ⁄4 to 1 ⁄2, depending on the nearest neighbor base pair, and that of dGMP (f G ) increased 1.1-5.6-fold. Thus, the increase in the replication error frequency (f G /f A for fU versus T) was 3.1-14.3-fold. The misincorporation rate of dGMP opposite fU (pK a ‫؍‬ 8.6) but not T (pK a ‫؍‬ 10.0) increased with pH (7.2-8.6) of the reaction mixture, indicating the participation of the ionized (or enolate) form of fU in the mispairing with G. The resulting mismatched fU:G primer terminus was more efficiently extended than the T:G terminus (8.2-11.3-fold). These results show that when T is oxidized to fU in DNA, fU promotes both misincorporation of dGMP at this site and subsequent elongation of the mismatched primer, hence potentially mutagenic.Faithful replication of DNA is essential for maintaining genetic integrity of living organisms. High fidelity of DNA replication is achieved by two cellular functions that involve discrimination of correct versus incorrect nucleotides by DNA polymerases (1, 2) and postreplication mismatch repair (3). The overall error frequency of DNA replication is one in 10 8 to 10 10 base pairs when they function properly. Fidelity of DNA replication also relies on the structural integrity of DNA itself that serves as a template for the newly synthesized strand. A number of endogenous and exogenous agents have been identified to induce structural deterioration of DNA (4). Among them, reactive oxygen species generate a very complicated spectrum of DNA damage (5, 6). These lesions are mostly restored by the base excision repair pathway both in prokaryotic and eukaryotic cells, but if left unrepaired, they arrest DNA synthesis or direct misincorporation of nucleotides during DNA replication, hence exerting deleterious effects on cells (7,8). Replication blocks and nucleotide misincorporation have been related to lethality and mutation of cells, respectively, until recently. However, this concept is now challenged by the discovery of numerous error-prone and error-free DNA polymerases that can bypass the blocking lesions (9). Although the past several years have witnessed the discovery...

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Peroxy Radical Oxidation of Thymidine

Cited by 49 publications

References 57 publications

Low energy electron stimulated desorption from DNA films dosed with oxygen

Low energy electron stimulated desorption from DNA films dosed with oxygen

Hepatoprotective effects and HSV-1 activity of the hydroethanolic extract ofCecropia glaziovii(embaúba-vermelha) against acyclovir-resistant strain

Oxidation of Thymine to 5-Formyluracil in DNA Promotes Misincorporation of dGMP and Subsequent Elongation of a Mismatched Primer Terminus by DNA Polymerase

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