Reactions of Small Reactive Species with<scp>DNA</scp>

Geacintov, Nicholas E.; Shafirovich, Vladimir

doi:10.1002/9781119953678.rad040

Cited by 7 publications

(10 citation statements)

References 254 publications

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“…A positive correlation between the increase in the iNOS expression levels and the accumulation of DNA damage has been reported [ 50 , 56 , 57 ]. It is well known that iNOS protein is responsible for the production of cellular nitric oxide (NO • ), which, reacting with superoxide radical anion (O 2 •– ), forms peroxynitrite (ONOO − ) (see Appendix A Figure A2 ) [ 28 ]. ONOO − is able to directly generate 8-oxo-Pu lesions, or, associated with its protonated form, decomposes spontaneously forming HO • and • NO 2 radicals.…”

Section: Discussionmentioning

confidence: 99%

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Oxygen-Dependent Accumulation of Purine DNA Lesions in Cockayne Syndrome Cells

Krokidis

D’Errico

Pascucci

et al. 2020

Cells

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Cockayne Syndrome (CS) is an autosomal recessive neurodegenerative premature aging disorder associated with defects in nucleotide excision repair (NER). Cells from CS patients, with mutations in CSA or CSB genes, present elevated levels of reactive oxygen species (ROS) and are defective in the repair of a variety of oxidatively generated DNA lesions. In this study, six purine lesions were ascertained in wild type (wt) CSA, defective CSA, wtCSB and defective CSB-transformed fibroblasts under different oxygen tensions (hyperoxic 21%, physioxic 5% and hypoxic 1%). In particular, the four 5′,8-cyclopurine (cPu) and the two 8-oxo-purine (8-oxo-Pu) lesions were accurately quantified by LC-MS/MS analysis using isotopomeric internal standards after an enzymatic digestion procedure. cPu levels were found comparable to 8-oxo-Pu in all cases (3–6 lesions/106 nucleotides), slightly increasing on going from hyperoxia to physioxia to hypoxia. Moreover, higher levels of four cPu were observed under hypoxia in both CSA and CSB-defective cells as compared to normal counterparts, along with a significant enhancement of 8-oxo-Pu. These findings revealed that exposure to different oxygen tensions induced oxidative DNA damage in CS cells, repairable by NER or base excision repair (BER) pathways. In NER-defective CS patients, these results support the hypothesis that the clinical neurological features might be connected to the accumulation of cPu. Moreover, the elimination of dysfunctional mitochondria in CS cells is associated with a reduction in the oxidative DNA damage.

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Section: Discussionmentioning

confidence: 99%

“…Among ROS, the hydroxyl radical (HO • ) is the most reactive species (cf. Appendix A Figure A2 ) [ 27 , 28 , 29 ]. Purine 5′,8-cyclo-2′-deoxynucleosides (short name: 5′,8-cyclopurine; acronym: cPu) are well recognized products of nucleic acid damage [ 30 , 31 , 32 , 33 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

Oxygen-Dependent Accumulation of Purine DNA Lesions in Cockayne Syndrome Cells

Krokidis

D’Errico

Pascucci

et al. 2020

Cells

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“…The overproduction of ROS/RNS has been linked with the etiology of many diseases. The main processes that generate HO • radicals are depicted in reactions (1)–(3): the Fenton reaction of H 2 O 2 , the reduction of HOCl by the superoxide radical anion, and the spontaneous decomposition of protonated ONOO – , respectively [2,3]. H 2 O 2 + Fe 2+ → Fe 3+ + HO − + HO • HOCl + O 2 •− → O 2 + Cl − + HO • ONOO − + H + ⇆ ONOOH → • NO 2 + HO • …”

Section: Introductionmentioning

confidence: 99%

5′,8-Cyclopurine Lesions in DNA Damage: Chemical, Analytical, Biological, and Diagnostic Significance

Chatgilialoglu

Ferreri

Geacintov

et al. 2019

Cells

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Purine 5′,8-cyclo-2′-deoxynucleosides (cPu) are tandem-type lesions observed among the DNA purine modifications and identified in mammalian cellular DNA in vivo. These lesions can be present in two diasteroisomeric forms, 5′R and 5′S, for each 2′-deoxyadenosine and 2′-deoxyguanosine moiety. They are generated exclusively by hydroxyl radical attack to 2′-deoxyribose units generating C5′ radicals, followed by cyclization with the C8 position of the purine base. This review describes the main recent achievements in the preparation of the cPu molecular library for analytical and DNA synthesis applications for the studies of the enzymatic recognition and repair mechanisms, their impact on transcription and genetic instability, quantitative determination of the levels of lesions in various types of cells and animal model systems, and relationships between the levels of lesions and human health, disease, and aging, as well as the defining of the detection limits and quantification protocols.

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“…The hydroxyl radical (HO ) is a potent oxidant that reacts at near diffusion-limited rates with most biomolecules, including nucleic acids [1]. This radical is produced in biological systems through oxygen metabolism; however, several well-recognized exogenous factors, e.g.…”

Section: Introductionmentioning

confidence: 99%

“…This radical is produced in biological systems through oxygen metabolism; however, several well-recognized exogenous factors, e.g. exposure to ionizing radiation or redox metal ion overload, are known to produce HO and related reactive oxygen species (ROS) [1]. With regard to DNA chemical reactivity, diffusible HO are known to either add to base moieties [2], with the majority of HO attacks occurring at this location, or abstract a Hatom from 2-deoxyribose units [3].…”

Section: Introductionmentioning

confidence: 99%

Radical-induced purine lesion formation is dependent on DNA helical topology

Terzidis

Prisecaru

Molphy

et al. 2016

Free Radical Research

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Herein we report the quantification of purine lesions arising from gamma-radiation sourced hydroxyl radicals (HO · ) on tertiary dsDNA helical forms of supercoiled (SC), open circular (OC), and linear (L) conformation, along with single-stranded folded and non-folded sequences of guanine-rich DNA in selected G-quadruplex structures. We identify that DNA helical topology and folding plays major, and unexpected, roles in the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and 8-oxo-7,8-dihydro-2'-deoxyadenosine (8-oxo-dA), along with tandem-type purine lesions 5 (mutTel24) were exposed to HO · radicals and purine lesions were then quantified via stable isotope dilution LC-MS/MS analysis. Purine oxidation in dsDNA follows L > OC ) SC indicating greater damage towards the extended B-DNA topology. Conversely, G-quadruplex sequences were significantly more resistant toward purine oxidation in their unfolded states as compared with G-tetrad folded topologies; this effect is confirmed upon comparative analysis of Tel22 ($50% solution folded) and mutTel24 ($90% solution folded). In an effort to identify the accessibly of hydroxyl radicals to quadruplex purine nucleobases, G-quadruplex solvent cavities were then modeled at 1.33 Å with evidence suggesting that folded G-tetrads may act as potential oxidant traps to protect against chromosomal DNA damage. ARTICLE HISTORY

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Reactions of Small Reactive Species withDNA

Cited by 7 publications

References 254 publications

Oxygen-Dependent Accumulation of Purine DNA Lesions in Cockayne Syndrome Cells

Oxygen-Dependent Accumulation of Purine DNA Lesions in Cockayne Syndrome Cells

5′,8-Cyclopurine Lesions in DNA Damage: Chemical, Analytical, Biological, and Diagnostic Significance

Radical-induced purine lesion formation is dependent on DNA helical topology

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