DNA twisting flexibility and the formation of sharply looped protein-DNA complexes

DNA twisting flexibility and the formation of sharply looped protein-DNA complexes
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DOI:
10.1073/pnas.0409059102
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发表时间:
2005-03-08
影响因子:
11.1
通讯作者:
Widom, J
Widom, J
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Cloutier, TE;Widom, J

文献摘要

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基因调控复合物通常需要DNA结合蛋白质对通过环出短的(通常接近100 bp)DNA片段来相互作用。环可以在详细的长度和顺序上变化,因此,在总的螺旋扭曲中,这从根本上改变了它们的几何形状。如何在结构上适应这种可变性尚不清楚。在这里,我们表明,89- 105-bp的DNA圈的固有的扭曲性超过理论预期高达400倍。这些结果只能用DNA柔性的极大增强来解释,而不能用永久性弯曲来解释。它们使使用柔性的经典理论来理解尖锐的DNA环无效,但支持最近两个理论的预测。我们的研究结果意味着一个积极的作用,DNA的灵活性在环的形成,并建议,在详细的螺旋扭曲的调节环的可变性是自然容纳的固有的twistability的DNA。
Gene-regulatory complexes often require that pairs of DNA-bound proteins interact by looping-out short (often approximate to 100-bp) stretches of DNA. The loops can vary in detailed length and sequence and, thus, in total helical twist, which radically alters their geometry. How this variability is accommodated structurally is not known. Here we show that the inherent twistability of 89- to 105-bp DNA circles exceeds theoretical expectation by up to 400-fold. These results can be explained only by greatly enhanced DNA flexibility, not by permanent bends. They invalidate the use of classic theories of flexibility for understanding sharp DNA looping but support predictions of two recent theories. Our findings imply an active role for DNA flexibility in loop formation and suggest that variability in the detailed helical twist of regulatory loops is accommodated naturally by the inherent twistability of the DNA.