DNA topology influences p53 sequence-specific DNA binding through structural transitions within the target sites
DNA topology influences p53 sequence-specific DNA binding through structural transitions within the target sites
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DOI：
10.1042/bj20071648
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发表时间：
2008-05-15
影响因子：
4.1
通讯作者：
Fojta, Miroslav
中科院分区：
文献类型：
--
作者：
Jagelska, Eva B.;Brazda, Vaclav;Fojta, Miroslav
肿瘤抑制蛋白p53是响应于多种细胞应激信号而调节细胞增殖、分化和程序性细胞死亡的最重要的因子之一。P53是一种核磷蛋白，其生物化学功能与其以序列特异性方式结合DNA并作为转录因子起作用的能力密切相关。使用竞争分析，我们研究了DNA拓扑结构对人野生型p53蛋白的DNA结合的影响。我们制备了一组含有和不含p53靶序列的质粒DNA的拓扑异构体，它们的内部对称性不同。p53与DNA的结合随着负超螺旋密度（-σ）的增加而增加。Δ t-σ = 0.05与p53-DNA结合的额外增强相关。
The tumour suppressor protein p53 is one of the most important factors regulating cell proliferation, differentiation and programmed cell death in response to a variety of cellular stress signals. P53 is a nuclear phosphoprotein and its biochemical function is closely associated with its ability to bind DNA in a sequence-specific manner and operate as a transcription factor. Using a competition assay, we investigated the effect of DNA topology on the DNA binding of human wild-type p53 protein. We prepared sets of topoisomers of plasmid DNA with and without p53 target sequences, differing in their internal symmetry. Binding of p53 to DNA increased with increasing negative superhelix density (- sigma). At -sigma = 0.05 correlates with the extra enhancement of p53-DNA binding.