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Science 26 May 2000:
Vol. 288. no. 5470, pp. 1418 - 1421
DOI: 10.1126/science.288.5470.1418
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Reports

Mechanism of ATP-Dependent Promoter Melting by Transcription Factor IIH

Tae-Kyung Kim, 1 Richard H. Ebright, 2 Danny Reinberg 1*

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.

1 Howard Hughes Medical Institute, Division of Nucleic Acids Enzymology, Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
2 Howard Hughes Medical Institute, Waksman Institute, and Department of Chemistry, Rutgers University, Piscataway, NJ 08854, USA
*   To whom correspondence should be addressed. E-mail: reinbedf{at}umdnj.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)