UV damage in DNA promotes nucleosome unwrapping.
UV damage in DNA promotes nucleosome unwrapping.
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DOI：
10.1074/jbc.m110.140087
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发表时间：
2010-08-20
期刊：
影响因子：
--
通讯作者：
Smerdon MJ
中科院分区：
文献类型：
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作者：
Duan MR;Smerdon MJ
DNA与染色质中的组蛋白的缔合阻碍DNA修复酶接近DNA损伤。核小体存在于动态平衡中，其中部分DNA分子自发地解开，暂时暴露出埋藏的DNA位点。因此，在染色质的某些区域中的核小体动力学可以提供有效修复埋藏的DNA损伤所需的暴露时间和空间。我们已经使用FRET和限制性内切酶的可及性研究核小体动力学DNA损伤后，紫外线辐射。我们发现FRET效率以剂量依赖性方式降低，表明UV光产物的存在增强了组蛋白DNA的自发解包。此外，这种UV诱导的解包动力学变化与UV处理后组蛋白结合DNA的限制性内切酶可及性增加有关。令人惊讶的是，甚至在特定位点含有单个UV损伤的核小体核心颗粒中也观察到了增加的解包裹动力学。这些结果突出了核小体相关DNA损伤在染色质中增加“内在暴露”以修复蛋白质的潜力。
The association of DNA with histones in chromatin impedes DNA repair enzymes from accessing DNA lesions. Nucleosomes exist in a dynamic equilibrium in which portions of the DNA molecule spontaneously unwrap, transiently exposing buried DNA sites. Thus, nucleosome dynamics in certain regions of chromatin may provide the exposure time and space needed for efficient repair of buried DNA lesions. We have used FRET and restriction enzyme accessibility to study nucleosome dynamics following DNA damage by UV radiation. We find that FRET efficiency is reduced in a dose-dependent manner, showing that the presence of UV photoproducts enhances spontaneous unwrapping of DNA from histones. Furthermore, this UV-induced shift in unwrapping dynamics is associated with increased restriction enzyme accessibility of histone-bound DNA after UV treatment. Surprisingly, the increased unwrapping dynamics is even observed in nucleosome core particles containing a single UV lesion at a specific site. These results highlight the potential for increased “intrinsic exposure” of nucleosome-associated DNA lesions in chromatin to repair proteins.