RISS 검색 - 국내학술지논문

무료
기관 내 무료
유료

내보내기
내책장담기
한글로보기

정확도순

내림차순

내림차순

10개씩 출력

1
Translesion synthesis past guanine(C8)–thymine(N3) intrastrand cross-links catalyzed by selected A- and Y-family polymerases

Lee, Young-Ae,Lee, Yuan-Cho,Geacintov, Nicholas E.,Shafirovich, Vladimir The Royal Society of Chemistry 2016 Molecular bioSystems Vol.12 No.6
- 원문보기
Oxidatively generated guanine radicals in DNA can undergo various nucleophilic reactions including the formation of C8-guanine cross-links with adjacent or nearby N3-thymines in DNA in the presence of O-2. These G[8-3]T lesions have been identified in the DNA of human cells exposed to oxidative stress, and are most likely genotoxic if not removed by cellular defence mechanisms. The abilities of several representative polymerases to bypass the G[8-3]T lesions in two different sequence contexts, G*T* and G*CT*, were assessed in vitro. The polymerase BF (bacillus fragment) from Bacillus stearothermophilus, the Y-family archaeal polymerases Dpo4 from Sulfolobus sulfataricus P2, and human DNA pol kappa and pol eta were selected for the study. The A-family polymerase BF was strongly blocked, while relatively weak translesion synthesis was observed in the case of Y-family polymerases Dpo4 and pol k. Primer extension catalyzed by pol eta was also partially stalled at various positions at or near the G[8-3]T crosslinked bases, but a significant and distributive primer extension was observed beyond the sites of the lesions with the efficiency being consistently greater in the case of G*CT* than in the case of G*T* lesions. The results obtained with pol eta are compared with translesion synthesis past other intrastrand cross-linked lesions with previously published results of others that include the isomeric G[8-5m]T lesions generated by ionizing radiation, the cis-syn cyclobutane pyrimidine dimer and the 6-4 photoproduct generated by UV irradiation, and the Pt-G*G* lesions derived from the reactions of the chemotherapeutic agent cisplatin with DNA.
2
Mechanisms of Oxidation of Guanine in DNA by Carbonate Radical Anion, a Decomposition Product of Nitrosoperoxycarbonate

Lee, Young ,Ae,Yun, Byeong ,Hwa,Kim, Seog ,K.,Margolin, Yelena,Dedon, Peter ,C.,Geacintov, Nicholas ,E.,Shafirovich, Vladimir WILEY-VCH Verlag 2007 Chemistry Vol.13 No.16
- 원문보기
Peroxynitrite is produced during inflammation and combines rapidly with carbon dioxide to yield the unstable nitrosoperoxycarbonate, which decomposes (in part) to CO3.− and .NO2 radicals. The CO3.− radicals oxidize guanine bases in DNA through a one-electron transfer reaction process that ultimately results in the formation of stable guanine oxidation products. Here we have explored these mechanisms, starting with a spectroscopic study of the kinetics of electron transfer from 20–22mer double-stranded oligonucleotides to CO3.− radicals, together with the effects of base sequence on the formation of the end-products in runs of one, two, or three contiguous guanines. The distributions of these alkali-labile lesions were determined by gel electrophoresis methods. The cascade of events was initiated through the use of 308 nm XeCl excimer laser pulses to generate CO3.− radicals by an established method based on the photodissociation of persulfate to sulfate radicals and the oxidation of bicarbonate. Although the Saito model (Saito et al., J. Am. Chem. Soc. 1995, 117, 6406–6407) predicts relative ease of one-electron oxidations in DNA, following the trend 5′-⋅⋅⋅GGG⋅⋅⋅ > 5′-⋅⋅⋅GG⋅⋅⋅ > 5′-⋅⋅⋅G⋅⋅⋅, we found that the rate constants for CO3.−-mediated oxidation of guanines in these sequence contexts (k5) showed only small variation within a narrow range [(1.5–3.0)×107 M−1 s−1]. In contrast, the distributions of the end-products are dependent on the base sequence context and are higher at the 5′-G in 5′-⋅⋅⋅GG⋅⋅⋅ sequences and at the first two 5′-guanines in the 5′-⋅⋅⋅GGG⋅⋅⋅ sequences. These effects are attributed to a combination of initial hole distributions among the contiguous guanines and the subsequent differences in chemical reaction yields at each guanine. The lack of dependence of k5 on sequence context indicates that the one-electron oxidation of guanine in DNA by CO3.− radicals occurs by an inner-sphere mechanism. Graphic Abstract Rates of one-electron oxidation of guanine in DNA by carbonate radicals do not depend on sequence context: The sequence-dependent damage at guanine sites (see figure) is attributed to a combination of initial hole distributions among the contiguous guanines and the subsequent differences in chemical reaction yields at each guanine. <img src='wiley_img/09476539-2007-13-16-CHEM200601434-content.gif' alt='wiley_img/09476539-2007-13-16-CHEM200601434-content'>

내보내기
내책장담기
한글로보기

정확도순

내림차순

내림차순

10개씩 출력

맨처음 페이지로 1 맨끝 페이지로

상세검색

RISS 보유자료

상세검색

해외전자자료

연관 검색어 추천