Zhou Chuanzheng, Greenberg Marc M
Department of Chemistry, Johns Hopkins University , 3400 North Charles Street, Baltimore, Maryland 21218, United States.
J Am Chem Soc. 2014 May 7;136(18):6562-5. doi: 10.1021/ja501285s. Epub 2014 Apr 22.
Although DNA binding proteins shield the genetic material from diffusible reactive oxygen species by reacting with them, the resulting protein (peroxyl) radicals can oxidize the bound DNA. To explore this possible DNA damage by protein radicals, histone H4 proteins containing an azoalkane radical precursor at defined sites were prepared. Photolysis of a nucleosome core particle containing the modified protein produces DNA damage that is consistent with selective C4'-oxidation. The nucleotide(s) damaged is highly dependent on proximity to the protein radical. These experiments provide insight into the effects of oxidative stress on protein-bound DNA, revealing an additional layer of complexity concerning nucleic acid damage.
尽管DNA结合蛋白通过与可扩散的活性氧反应来保护遗传物质，但由此产生的蛋白质（过氧）自由基可氧化结合的DNA。为了探究蛋白质自由基可能造成的这种DNA损伤，制备了在特定位点含有偶氮烷烃自由基前体的组蛋白H4。含有修饰蛋白的核小体核心颗粒的光解会产生与选择性C4'-氧化一致的DNA损伤。受损的核苷酸高度依赖于与蛋白质自由基的接近程度。这些实验深入了解了氧化应激对与蛋白质结合的DNA的影响，揭示了核酸损伤方面的另一层复杂性。
