CHANGES IN NUCLEAR-PROTEIN ACETYLATION IN UV-DAMAGED HUMAN-CELLS
CHANGES IN NUCLEAR-PROTEIN ACETYLATION IN UV-DAMAGED HUMAN-CELLS
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DOI：
10.1093/carcin/7.7.1087
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发表时间：
1986-07-01
期刊：
影响因子：
4.7
通讯作者：
SMERDON, MJ
中科院分区：
文献类型：
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作者：
RAMANATHAN, B;SMERDON, MJ
我们已经研究了在u. v.中核蛋白乙酰化的水平-辐射过的人成纤维细胞。最初，我们测量了总酸溶性核蛋白的乙酰化水平，并观察到两个不同的照射和未照射（对照）细胞之间的差异。照射后立即出现蛋白质超乙酰化的“波”（即总乙酰化水平高于未照射细胞），持续2-6小时，具体取决于实验条件。 然后，该超乙酰化阶段之后是低乙酰化阶段，持续数小时，并且乙酰化的总水平直到u. v.损伤后24-72小时才恢复到对照细胞的水平。每个阶段的幅度和持续时间都取决于所使用的紫外光的剂量。超乙酰化波在低u. v.剂量（即< 5 J/m2）下更明显，而低乙酰化波在较高u. v.剂量（≥ 5 J/m2）下更明显。8 J/m2）。此外，当细胞暴露于2 mM羟基脲时，每个阶段的持续时间延长，所述2 mM羟基脲是一种在u. v.受损网站个别核蛋白的乙酰化水平的检查表明，乙酰化的核心组蛋白遵循相同的模式观察到的总酸溶性蛋白馏分。此外，这些是观察到的总酸溶性部分中唯一的主要蛋白质，在紫外线损伤后立即发生早期快速的超乙酰化。组蛋白H1的乙酰化在受损细胞和对照细胞中都可以忽略不计，而三种突出的非组蛋白蛋白在每种情况下仅在长标记时间（> 4小时）后才被乙酰化，在u. v.受损细胞这些结果提出了一种可能性，即在人类细胞中，核蛋白乙酰化和DNA的核苷酸切除修复之间存在因果关系。
We have investigated the levels of nuclear protein acetylation in u.v.-irradiated human fibroblasts. Initially, we measured the levels of acetylation in total acid-soluble nuclear proteins and observed two distinct differences between the irradiated and unirradiated (control) cells. Immediately after irradiation, there is a ''wave'' of protein hyperacetylation (i.e. a total acetylation level greater than that of unirradiated cells) that lasts for 2-6 h depending on the experimental conditions. This hyperacetylation phase is then followed by a hypoacetylation phase, lasting for many hours, and the total level of acetylation does not return to that of control cells until 24-72 h after u.v. damage. Both the magnitude and duration of each phase is dependent on the dose of u.v. light used. The wave of hyperacetylation is more pronounced at low u.v. doses (i.e. < 5 J/m2), while the wave of hypoacetylation is more pronounced at higher u.v. doses (.gtoreq. 8 J/m2). Furthermore, the duration of each phase is prolonged when cells are exposed to 2 mM hydroxyurea, an agent which retards the rate of excision repair at u.v.-damaged sites. Examination of the acetylation levels of the individual nuclear proteins indicated that acetylation of the core histones follows the same pattern observed for the total acid-soluble protein fractions. Furthermore, these were the only major proteins in the total acid-soluble fraction observed to undergo the early, rapid hyperacetylation immediately following u.v. damage. Acetylation of histone H1 was negligible in both damaged and control cells, while three prominent non-histone proteins were acetylated only after long labeling times (> 4 h) in each case, gradually becoming hyperacetylated in the u.v.-damaged cells. These results raise the possibility that a causal relationship exists between nuclear protein acetylation and nucleotide excision repair of DNA in human cells.