Mechanism of ATP-dependent promoter melting by transcription factor IIH

Mechanism of ATP-dependent promoter melting by transcription factor IIH
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DOI:
10.1126/science.288.5470.1418
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发表时间:
2000-05-26
期刊:
影响因子:
56.9
通讯作者:
Reinberg, D
Reinberg, D
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kim, TK;Ebright, RH;Reinberg, D

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我们发现,转录因子IIH ERCC3亚基是一种DNA解旋酶,负责在转录起始过程中熔化依赖于三磷酸腺苷(ATP)的启动子,它不与熔化的启动子区域相互作用,而是与该区域下游的DNA相互作用。我们进一步表明,启动子融化不会改变融化区域上游的蛋白质-DNA相互作用,但会改变该区域内部和下游的相互作用。我们的结果排除了IIH通过传统的DNA解旋酶机制在启动子融化中发挥作用的假设。我们认为IIH的功能类似于分子扳手:相对于固定的上游蛋白质-DNA相互作用旋转下游DNA,从而产生扭矩并融化介于其间的DNA。
We show that transcription factor IIH ERCC3 subunit, the DNA helicase responsible for adenosine triphosphate (ATP)-dependent promoter melting during transcription initiation, does not interact with the promoter region that undergoes melting but instead interacts with DNA downstream of this region. We show further that promoter melting does not change protein-DNA interactions upstream of the region that undergoes melting but does change interactions within and downstream of this region. Our results rule out the proposal that IIH functions in promoter melting through a conventional DNA-helicase mechanism. We propose that IIH functions as a molecular wrench: rotating downstream DNA relative to fixed upstream protein-DNA interactions, thereby generating torque on, and melting, the intervening DNA.