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首页> 外文期刊>Molecular and Cellular Biology >Gadd45, a p53-Responsive Stress Protein, Modifies DNA Accessibility on Damaged Chromatin
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Gadd45, a p53-Responsive Stress Protein, Modifies DNA Accessibility on Damaged Chromatin

机译:Gadd45是一种p53反应性应激蛋白,可修饰受损染色质的DNA可及性

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This report demonstrates that Gadd45, a p53-responsive stress protein, can facilitate topoisomerase relaxing and cleavage activity in the presence of core histones. A correlation between reduced expression of Gadd45 and increased resistance to topoisomerase I and topoisomerase II inhibitors in a variety of human cell lines was also found. Gadd45 could potentially mediate this effect by destabilizing histone-DNA interactions since it was found to interact directly with the four core histones. To evaluate this possibility, we investigated the effect of Gadd45 on preassembled mononucleosomes. Our data indicate that Gadd45 directly associates with mononucleosomes that have been altered by histone acetylation or UV radiation. This interaction resulted in increased DNase I accessibility on hyperacetylated mononucleosomes and substantial reduction of T4 endonuclease V accessibility to cyclobutane pyrimidine dimers on UV-irradiated mononucleosomes but not on naked DNA. Both histone acetylation and UV radiation are thought to destabilize the nucleosomal structure. Hence, these results imply that Gadd45 can recognize an altered chromatin state and modulate DNA accessibility to cellular proteins.
机译:该报告证明,在核心组蛋白存在下,p53反应性应激蛋白Gadd45可以促进拓扑异构酶的松弛和裂解活性。还发现在多种人类细胞系中,Gadd45的表达降低与对拓扑异构酶I和拓扑异构酶II抑制剂的耐药性增加之间存在相关性。由于发现Gadd45与四个核心组蛋白直接相互作用,因此它可能通过破坏组蛋白与DNA的相互作用来介导这种作用。为了评估这种可能性,我们研究了Gadd45对预组装单核小体的影响。我们的数据表明,Gadd45与已被组蛋白乙酰化或UV辐射改变的单核小体直接缔合。这种相互作用导致在超乙酰化的单核小体上增加DNase I的可及性,并在紫外线照射的单核小体上显着降低T4核酸内切酶V对环丁烷嘧啶二聚体的可及性,而在裸露的DNA上则没有。组蛋白乙酰化和紫外线辐射都被认为会破坏核小体结构的稳定性。因此,这些结果表明,Gadd45可以识别染色质状态的改变并调节DNA对细胞蛋白的可及性。

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