Nature 368, 769 - 772 (21 April 1994); doi:10.1038/368769a0

Dual role of TFIIH in DNA excision repair and in transcription by RNA polymerase II

Ronny Drapkin^*, Joyce T. Reardon^†, Athar Ansari^*, Juch-Chin Huang^†, Leigh Zawel^*, KyuJeong Ahn^†, Aziz Sancar^† & Danny Reinberg^*‡

^* Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 675 Hoes Lane, Piscataway, New Jersey 08854-5635, USA
^† Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
^‡ To whom correspondence should be addressed.

THE RNA polymerase II general transcription factor TFIIH is composed of several polypeptides. The observation that the largest subunit of TFIIH is the excision-repair protein XPB/ERCC3 (ref. 1), a helicase implicated in the human DNA-repair disorders xeroderma pigmentosum (XP) and Cockayne's syndrome^2,3, suggests a functional link between transcription and DNA repair^4,5. To understand the connection between these two cellular processes, we have extensively purified and functionally analysed TFIIH. We find that TFIIH has a dual role, being required for basal transcription of class II genes and for participation in DNA-excision repair. TFIIH is shown to complement three different cell extracts deficient in excision repair: XPB/ERCC3, XPC and XPD/ ERCC2. The complementation of XPB and XPD is a consequence of ERCC3 and ERCC2 being integral subunits of TFIIH, whereas complementation of XPC is due to an association of this polypeptide with TFIIH. We found that the general transcription factor IIE negatively modulates the helicase activity of TFIIH through a direct interaction between TFIIE and the ERCC3 subunit of TFIIH.

References

1.	Schaeffer, L. et al. Science 260, 58−63 (1993). | PubMed | ChemPort |
2.	Cleaver, J. E. & Kraemer, K. H. in The Metabolic Basis of Inherited Disease (eds Scriver, C. R. et al.) 6 edn 2949−2971 (McGraw-Hill, New York, 1989).
3.	Weeda, G. et al. Cell 62, 777−791 (1990). | Article | PubMed | ISI | ChemPort |
4.	Hanawalt, P. Mellon, I. Curr. Biol. 3, 67−69 (1993). | Article | PubMed | ISI | ChemPort |
5.	Selby, C. P. & Sancar, A. Science 260, 53−57 (1993). | PubMed | ISI | ChemPort |
6.	Fisher, L. et al. Science 257, 1392−1394 (1992). | PubMed |
7.	Inostroza, J., Flores, O. & Reinberg, D. J. biol. Chem. 266, 9304−9308 (1991). | PubMed | ChemPort |
8.	Peterson, M. G. et al. Nature 354, 369−373 (1991). | Article | PubMed | ISI | ChemPort |
9.	Ohkuma, Y. et al. Nature 354, 398−401 (1991). | Article | PubMed | ISI | ChemPort |
10.	Guzder, S. N. et al. Nature 367, 91−94 (1994). | Article | PubMed | ISI | ChemPort |
11.	Qui, H., Park, E., Prakash, L. & Prakash, S. Genes Dev. 7, 2161−2171 (1993). | PubMed | ISI | ChemPort |
12.	Huang, J.-C., Svoboda, D. L., Reardon, J. T. & Sancar, A. Proc. natn. Acad. Sci. U.S.A. 89, 3664−3668 (1992). | ChemPort |
13.	Sancar, A. & Tang, M. S. Photochem. Photobiol. 57, 905−921 (1993). | PubMed | ChemPort |
14.	Tanaka, K. & Wood, R. D. Trends biochem. Sci. 19, 83−86 (1994). | Article | PubMed | ChemPort |
15.	Drapkin, R., Sancar, A. & Reinberg, D. Cell 77, 9−12 (1994). | Article | PubMed | ISI | ChemPort |
16.	Prakash, S., Sung, P. & Prakash, L. A. Rev. Genet. 27, 33−70 (1993). | Article | ChemPort |
17.	Li, L., Bales, E. S., Peterson, C. A. & Legerski, R. J. Nature Genet. 5, 413−417 (1993). | Article | PubMed | ChemPort |
18.	Legerski, R. J. & Peterson, C. A. Nature 359, 70−73 (1992). | Article | PubMed | ChemPort |
19.	Sung, P. et al. Nature 365, 852−855 (1993). | Article | PubMed | ISI | ChemPort |
20.	Lu, H., Zawel, L., Fisher, L., Egly, J. M. & Reinberg, D. Nature 358, 641−645 (1992). | Article | PubMed | ISI | ChemPort |
21.	Matson, S. W., Bean, D. W. & George, J. W. Bioessays 16, 13−22 (1994). | Article | PubMed | ISI | ChemPort |
22.	Sumimoto, H. et al. Nature 354, 401−404 (1991). | Article | PubMed | ISI | ChemPort |
23.	Zawel, L., Lu, H., Cisek, L. J., Corden, J. L. Reinberg, D. Cold Spring Harbor Symp. quant. Biol. 58, 187−198 (1993). | PubMed | ChemPort |
24.	Friedberg, E. C. Cell 71, 887−889 (1992). | Article | PubMed | ChemPort |
25.	Reardon, J. T., Thompson, L. H. & Sancar, A. Cold Spring Harbor Symp. quant. Biol. 58, 605−617 (1993). | PubMed | ChemPort |
26.	Flores, O., Lu, H. & Reinberg, D. J. biol. Chem. 267, 2786−2793 (1992). | PubMed | ISI | ChemPort |
27.	Ha, I., Lane, W. S. & Reinberg, D. Nature 352, 689−695 (1991). | Article | PubMed | ChemPort |
28.	Manley, J. L., Fire, A., Cano, A., Sharp, P. A. & Gefter, M. L. Proc. natn. Acad. Sci. U.S.A. 77, 3855−3859 (1980). | ChemPort |