Reactions of Reactive Nitrogen Species and Carbonate Radical Anions with DNA

Shafirovich, Vladimir; Crean, Conor; Geacintov, Nicholas E.

doi:10.1002/9780470526279.ch11

Cited by 7 publications

(13 citation statements)

References 122 publications

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“…2,13 The first pathway suggests a correlation of the product yields with the solution pH, which can affect nucleophilicity/electrophilicity of the reaction partners. In turn, the reactivities of radicals (CO 3 •− or SO 4 •− ) can affect product formation via the radical combination.…”

Section: Resultsmentioning

confidence: 99%

Lifetimes and Reaction Pathways of Guanine Radical Cations and Neutral Guanine Radicals in an Oligonucleotide in Aqueous Solutions

2012

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The exposure of guanine in the oligonucleotide 5’-d(TCGCT) to one-electron oxidants leads initially to the formation of the guanine radical cation G•+, its deptotonation product G(−H)• and, ultimately, to various two- and four-electron oxidation products via pathways that depend on the oxidants and reaction conditions. We utilized single or successive multiple laser pulses (308 nm, 1 Hz rate) to generate the oxidants CO3•− and SO4•− (via the photolysis of S2O82− in aqueous solutions in the presence and absence of bicarbonate, respectively) at concentrations/pulse that were ~20-fold lower than the concentration of 5’-d(TCGCT). Time-resolved absorption spectroscopy measurements following single-pulse excitation show that the G•+ radical (pKa = 3.9) can be observed only at low pH and is hydrated within ≥ 3 ms at pH 2.5, thus forming the two-electron oxidation product 8-oxo-7,8-dihydroguanosine (8-oxoG). At neutral pH, and single pulse excitation, the principal reactive intermediate is G(−H)• that at best, reacts only slowly with H2O, and lives for ≥ 70 ms in the absence of oxidants/other radicals to form base sequence-dependent intrastrand cross-links via the nucleophilic addition of N3-thymidine to C8-guanine (5'-G*CT* and 5'-T*CG*). Alternatively, G(−H)• can be oxidized further by reaction with CO3•− generating the two electron products 8-oxoG (C8 addition), and 5-carboxamido-5-formamido-2-iminohydantoin (2Ih, by C5 addition). The four-electron oxidation products, guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp), appear only after a second (or more) laser pulses. The levels of all products, except 8-oxoG, which remains at a low constant value, increase with the number of laser pulses.

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Section: Resultsmentioning

confidence: 99%

Lifetimes and Reaction Pathways of Guanine Radical Cations and Neutral Guanine Radicals in an Oligonucleotide in Aqueous Solutions

2012

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“…61, 62 The well-known example of nucleophilic addition to guanine radical is hydration of G •+ radicals. 61 The experimental evidence for this reaction was provided by the insertion of isotopic 18 O in 8-oxo-7,8-dihydroguanine (8-oxoG) during the riboflavin photosensitized oxidation of calf thymus DNA in H 2 18 O solutions.…”

Section: Resultsmentioning

confidence: 99%

Proton-coupled hole hopping in nucleosomal and free DNA initiated by site-specific hole injection

Liu

Geacintov

et al. 2012

Phys. Chem. Chem. Phys.

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Nucleosomes were reconstituted from recombinant histones and a 147-mer DNA sequence containing the damage reporter sequence 5′-…d([2AP]T[GGG]1TT[GGG]2TTT[GGG]3TAT)… with 2-aminopurine (2AP) at position 27 from the dyad axis. Footprinting studies with •OH radicals reflect the usual effects of “in” and “out” rotational settings, while, interestingly, the guanine oxidizing one-electron oxidant CO3•− radical does not. Site-specific hole injection was achieved by 308 nm excimer laser pulses to produce 2AP•+ cations, and superoxide via the trapping of hydrated electrons. Rapid deprotonation (~ 100 ns) and proton coupled electron transfer generates neutral guanine radicals, G(−H)• and hole hopping between the three groups of [GGG] on micro- to millisecond time scales. Hole transfer competes with hole trapping that involves the combination of O2•− with G(−H)• radicals to yield predominantly 2,5-diamino-4H-imidazolone (Iz) and minor 8-oxo-7,8-dihydroguanine (8-oxoG) end-products in free DNA (Misiaszek et al. J. Biol. Chem. 2004, 279, 32106). Hole migration is less efficient in nucleosomal than in the identical protein-free DNA by a factor of 1.2 – 1.5. The Fpg/piperidine strand cleavage ratio is ~1.0 in free DNA at all three GGG sequences and at the “in” rotational settings [GGG]1,3 facing the histone core, and ~2.3 at the “out” setting at [GGG]2 facing away from the histone core. These results are interpreted in terms of competitive reaction pathways of O2•− with G(−H)• radicals at the C5 (yielding Iz) and C8 (yielding 8-oxoG) positions. These differences in product distributions are attributed to variations in the local nucleosomal B-DNA base pair structural parameters that are a function of surrounding sequence context and rotational setting.

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“…The O 2˙À radicals derived from the reduction of oxygen by 8-HO-G˙radicals can rapidly combine with G(-H)˙radicals with the formation of imidazolone lesions (27,(29)(30)(31). Our laser flash photolysis experiments showed that the rate constant of reaction of O 2˙À with G(-H)˙, site-specifically positioned in the DNA duplex is 4.7 9 10 8 M À1 s À1 (27,(29)(30)(31). In typical laser flash photolysis experiments, the combination of G(-H)ȧ nd O 2˙À occurs on characteristic time scales of 0.3-0.5 ms and contributes to the observed decay of G(-H)˙(the ms component in Fig.…”

Section: Discussionmentioning

confidence: 99%

Generation of 8‐oxo‐7,8‐dihydroguanine in G‐Quadruplexes Models of Human Telomere Sequences by One‐electron Oxidation

Merta

Geacintov

Shafirovich

2018

Photochem & Photobiology

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The mechanistic aspects of one-electron oxidation of G-quadruplexes in the basket (Na ions) and hybrid (K ions) conformations were investigated by transient absorption laser kinetic spectroscopy and HPLC detection of the 8-oxo-7,8-dihydroguanine (8-oxoG) oxidation product. The photo-induced one-electron abstraction from G-quadruplexes was initiated by sulfate radical anions (SO ˙ ) derived from the photolysis of persulfate ions by 308 nm excimer laser pulses. In neutral aqueous solutions (pH 7.0), the transient absorbance of neutral guanine radicals, G(-H)˙, is observed following the complete decay of SO ˙ radicals (~10 μs after the actinic laser flash). In both basket and hybrid conformations, the G(-H)˙ decay is biphasic with one component decaying with a lifetime of ~0.1 ms, and the other with a lifetime of 20-30 ms. The fast decay component (~0.1 ms) in G-quadruplexes is correlated with the formation of 8-oxoG lesions. We propose that in G-quadruplexes, G(-H)˙ radicals retain radical cation character by sharing the N1-proton with the O -atom of G in the [G˙ : G] Hoogsteen base pair; this [G(-H)˙: H G ⇄ G˙ : G] leads to the hydration of G˙ radical cation within the millisecond time domain, and is followed by the formation of the 8-oxoG lesions.

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Reactions of Reactive Nitrogen Species and Carbonate Radical Anions with DNA

Cited by 7 publications

References 122 publications

Lifetimes and Reaction Pathways of Guanine Radical Cations and Neutral Guanine Radicals in an Oligonucleotide in Aqueous Solutions

Lifetimes and Reaction Pathways of Guanine Radical Cations and Neutral Guanine Radicals in an Oligonucleotide in Aqueous Solutions

Proton-coupled hole hopping in nucleosomal and free DNA initiated by site-specific hole injection

Generation of 8‐oxo‐7,8‐dihydroguanine in G‐Quadruplexes Models of Human Telomere Sequences by One‐electron Oxidation

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