Mapping three guanine oxidation products along DNA following exposure to three types of reactive oxygen species.
Mapping three guanine oxidation products along DNA following exposure to three types of reactive oxygen species.
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DOI：
10.1016/j.freeradbiomed.2018.04.561
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发表时间：
2018-06
影响因子：
7.4
通讯作者：
Tretyakova N
中科院分区：
文献类型：
--
作者：
Matter B;Seiler CL;Murphy K;Ming X;Zhao J;Lindgren B;Jones R;Tretyakova N
呼吸、炎症和免疫反应过程中产生的活性氧和氮会损害细胞 DNA，导致衰老、癌症和神经退行性变。氧化 DNA 碱基干扰 DNA 复制和转录的能力受到其化学结构和在基因组中的位置的强烈影响。在目前的工作中，我们研究了 Kras 原癌基因中局部 DNA 序列背景、DNA 二级结构和氧化剂特性对鸟嘌呤氧化效率和化学的影响。我们实验室开发的一种新型同位素标记策略用于准确绘制光氧化后沿 DNA 双链体形成的 2,2-二氨基-4-[(2-脱氧-β-D-呋喃红基)氨基]-5(2H)-恶唑酮 (Z)、8-氧代-7,8-二氢-2'-脱氧鸟苷 (OG) 和 8-硝基鸟嘌呤 (8-NO2-G) 损伤。核黄素的存在、亚硝基过氧碳酸酯的处理以及羟基自由基存在下的氧化。核黄素介导的光氧化优先诱导 GG 重复序列中 5' 鸟嘌呤处的 OG 损伤，而亚硝基过氧碳酸酯治疗则针对 GG 和 AG 二核苷酸中的 3'-鸟嘌呤。羟基自由基介导的氧化后观察到很少的序列选择性。然而，无论氧化剂身份如何，Z 和 8-NO2-G 加合物在双链体末端过量产生。总的来说，我们的结果表明，基因组中 Z、OG 和 8-NO2-G 加合物形成的模式是不同的，并且受到氧化剂身份和 DNA 二级结构的影响。
Reactive oxygen and nitrogen species generated during respiration, inflammation, and immune response can damage cellular DNA, contributing to aging, cancer, and neurodegeneration. The ability of oxidized DNA bases to interfere with DNA replication and transcription is strongly influenced by their chemical structures and locations with the genome. In the present work, we examined the influence of local DNA sequence context, DNA secondary structure, and oxidant identity on the efficiency and the chemistry of guanine oxidation in the context of the Kras protooncogene. A novel isotope labeling strategy developed in our laboratory was used to accurately map the formation of 2,2-diamino-4-[(2-deoxy-β-D-erythropentofuranosyl)amino]-5(2H)-oxazolone (Z), 8-oxo-7,8-dihydro-2’-deoxyguanosine (OG), and 8-nitroguanine (8-NO2-G) lesions along DNA duplexes following photooxidation in the presence of riboflavin, treatment with nitrosoperoxycarbonate, and oxidation in the presence of hydroxyl radicals. Riboflavin-mediated photooxidation preferentially induced OG lesions at 5’ guanines within GG repeats, while treatment with nitrosoperoxycarbonate targeted 3’-guanines within GG and AG dinucleotides. Little sequence selectivity was observed following hydroxyl radical-mediated oxidation. However, Z and 8-NO2-G adducts were overproduced at duplex ends, irrespective of oxidant identity. Overall, our results indicate that the patterns of Z, OG, and 8-NO2-G adduct formation in the genome are distinct and are influenced by oxidant identity and the secondary structure of DNA.
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影响因子：
3.9
作者：
Greenberg, MM
通讯作者：
Greenberg, MM
影响因子：
56.9
作者：
DICKERSON, RE;DREW, HR;KOPKA, ML
通讯作者：
KOPKA, ML
影响因子：
3.3
作者：
Douki, T;Cadet, J
通讯作者：
Cadet, J
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作者：
An N;Fleming AM;Burrows CJ
通讯作者：
Burrows CJ
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作者：
Bhamra, Inder;Compagnone-Post, Patricia;Cosstick, Richard
通讯作者：
Cosstick, Richard