Formation of 8-oxo-7,8-dihydroguanine-radicals in  -irradiated DNA by multiple one-electron oxidations

Shukla, Lata I.; Adhikary, Amitava; Pazdro, Robert; Becker, Dávid; Sevilla, Michael D.

doi:10.1093/nar/gkm083

Cited by 43 publications

(44 citation statements)

References 51 publications

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“…The Tl 3+ loading used (1/10 bp) is sufficient to thoroughly suppress the reductive-damage pathway (33) and allows observation of the formation of sugar radicals from photo-excited G• + (15). All samples were stored at 77 K.…”

Section: Methodsmentioning

confidence: 99%

“…After γ-irradiation, annealing and light illumination, the ice or glassy sample was immediately immersed in liquid nitrogen, and an ESR spectrum recorded at 77 K and 40 dB (20 µW) [(11,15,33) and the references therein]. Fremy's salt (with g = 2.0056, A N = 13.09 G) was used for field calibration.…”

Section: Methodsmentioning

confidence: 99%

“…The fractional compositions of radicals observed in experimental spectra were determined using least-square fittings of benchmark spectra with the help of programs (ESRPLAY and ESRADSUB) developed in our laboratory [(11,15,33) and the references therein]. A sharp singlet spike from irradiated quartz at g = 2.0006 was subtracted from all spectra before analysis.…”

Section: Methodsmentioning

confidence: 99%

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UVA-visible photo-excitation of guanine radical cations produces sugar radicals in DNA and model structures

Adhikary

Malkhasian

Collins

et al. 2005

Nucleic Acids Research

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305

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This work presents evidence that photo-excitation of guanine radical cations results in high yields of deoxyribose sugar radicals in DNA, guanine deoxyribonucleosides and deoxyribonucleotides. In dsDNA at low temperatures, formation of C1′• is observed from photo-excitation of G•+ in the 310–480 nm range with no C1′• formation observed ≥520 nm. Illumination of guanine radical cations in 2′dG, 3′-dGMP and 5′-dGMP in aqueous LiCl glasses at 143 K is found to result in remarkably high yields (∼85–95%) of sugar radicals, namely C1′•, C3′• and C5′•. The amount of each of the sugar radicals formed varies dramatically with compound structure and temperature of illumination. Radical assignments were confirmed using selective deuteration at C5′ or C3′ in 2′-dG and at C8 in all the guanine nucleosides/tides. Studies of the effect of temperature, pH, and wavelength of excitation provide important information about the mechanism of formation of these sugar radicals. Time-dependent density functional theory calculations verify that specific excited states in G•+ show considerable hole delocalization into the sugar structure, in accord with our proposed mechanism of action, namely deprotonation from the sugar moiety of the excited molecular radical cation.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

UVA-visible photo-excitation of guanine radical cations produces sugar radicals in DNA and model structures

Adhikary

Malkhasian

Collins

et al. 2005

Nucleic Acids Research

Self Cite

305

View full text Add to dashboard Cite

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“…are much more stable, mutagenic and lethal as compared to 8-oxoG. [12][13][14][15][16][17] These lesions can also be directly produced from guanine upon exposure of DNA to several oxidants such as singlet oxygen, 18 superoxide radical anions, 19 peroxynitrite 20 etc. 21 Further, depending upon the reaction environment e.g.…”

Section: Introductionmentioning

confidence: 99%

The R- and S-diastereoisomeric effects on the guanidinohydantoin-induced mutations in DNA

Jena

Gaur

Mishra

2015

Phys. Chem. Chem. Phys.

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Direct and indirect oxidation of guanine in DNA produces guanidinohydantoin (Gh), which is capable of inhibiting replication and inducing mutations during cellular activities. Although some biochemical studies have proposed that Gh may induce exclusively G to C mutations in DNA, other studies have predicted the occurrence of both G to C and G to T mutations. However, the exact reasons for these mutations and the dubious character of Gh in this context are not yet understood. Further, due to insufficient structural data, the electronic structure of Gh that can participate in the formation of different base pair complexes in DNA is also not known. Here, density functional theory (DFT) is used to find the most stable tautomers of Gh at the base level out of a total 112 possible tautomers and their involvement in mutagenesis is investigated by computing structures, energies and electronic properties of different base pair complexes formed between the syn- and anti-conformations of the most stable tautomer of Gh (aGh) and all the bases of DNA. It is found that aGh can coexist in R- and S-diastereoisomeric configurations. Due to the flexible guanidinium group, it can rotate about the N3-C4 bond in each of the above diastereoisomers to form two different stable conformations (aGh1 and aGh2). It is further shown that among the different base pair complexes involving aGh1, syn-aGh1:G is the most stable. This indicates that G would be easily incorporated against syn-aGh1 giving rise to G to C mutations in DNA. However, in the case of aGh2, G is the preferred base pair partner of syn-aGh2 and T is the preferred base pair partner of anti-aGh2. This implies that in addition to G to C mutations, the occurrence of aGh2 in DNA may also induce G to A mutations. Further, due to similarities between base pairing patterns and binding energies of syn-aGh1:A and syn-aGh2:A complexes with those of the T:A complex, DNA polymerases may mistakenly insert A opposite aGh1 or aGh2 by misrecognizing the latter as T. This may ultimately induce G to T mutations in DNA. However, as the constraints imposed by the DNA backbones and stacking interactions were not considered here, the possibilities of aGh2:T and aGh2:A base pairs need to be investigated experimentally. It is further found that the mutagenic character of aGh in the R- and S-diastereoisomeric forms is similar.

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“…8-oxo and 8-nitro derivatives of guanine and adenine are formed due to attack of OH Å , NO 2 Å or other ROS or RNOS on the bases or due to their ultraviolet or high energy irradiation [12,[20][21][22][23][24][25][26][27][28][29]. Oxidative modifications of DNA bases can also be produced due to nucleophilic attack of water molecule at the C8 site of the guanine radical cation leading to the formation of 8-hydroxyguanine radical which can transform to 8-oxoG [30]. Oxidation and nitration of the purine bases, particularly those of guanine, are known to cause mispairing of the bases and mutation which play key role in aging and various age-related degenerative diseases, including the Alzheimer's disease, diabetes, cardiovascular diseases and cancer.…”

Section: Introductionmentioning

confidence: 99%

Reactivities of radicals of adenine and guanine towards reactive oxygen species and reactive nitrogen oxide species: OH and NO2

Agnihotri

Mishra

2011

Chemical Physics Letters

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Formation of 8-oxo-7,8-dihydroguanine-radicals in -irradiated DNA by multiple one-electron oxidations

Cited by 43 publications

References 51 publications

UVA-visible photo-excitation of guanine radical cations produces sugar radicals in DNA and model structures

UVA-visible photo-excitation of guanine radical cations produces sugar radicals in DNA and model structures

The R- and S-diastereoisomeric effects on the guanidinohydantoin-induced mutations in DNA

Reactivities of radicals of adenine and guanine towards reactive oxygen species and reactive nitrogen oxide species: OH and NO2

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