Mrs. George A. Winzer Professor in Medicine and professor of structural biology at Stanford University Medical School, Department of Structural Biology, Stanford CA, U.S.A.
Research Interests : The fundamental basis of gene regulation, including the control of transcription as the first step in the pathway of gene expression, constitutes the research focus of Roger D. Kornberg.
In elucidating the inner workings of RNA, his research team has isolated the proteins responsible for transcription and gene regulation, including those that form a mediator to regulate the process. His research also helps explain how disease can result when transcription goes awry and offers the potential for unlocking new therapeutic approaches.
The goal of his team is to elucidate the fundamental basis of gene regulation. They study the control of transcription, the first step in the pathway of gene expression. Current work focuses on discovery of the molecular machines involved in transcription, reconstitution of the process with purified components, structure determination of the transcription machinery, and structure-function relationships in chromatin, the natural DNA template for transcription.
Highlights of work from the past three years include:
1. Discovery of a human homolog of the 20-protein yeast Mediator complex. Mediator is the central processing unit of gene regulation, receiving both positive and negative inputs and transducing the information to the transcription machinery.
2. Structure determination of 10-subunit, half million Dalton RNA polymerase II, in the act of transcription, with template DNA and product RNA, by X-ray crystallography at atomic resolution.
3. Structure determination of the entire transcription initiation complex by two-dimensional protein crystallography.
4. Discovery of a stably altered nucleosome produced by a purified chromatin-remodeling complex.
Current work is directed towards the structure of the entire transcription apparatus at atomic resolution and the mechanism of transcription control in living cells.
Awards and Honors : 2006 Nobel Prize in Chemistry "for his studies of the molecular basis of eukaryotic transcription"
His recent honors also include the General Motors Cancer Research Foundation’s Alfred P. Sloan Jr. Prize, the Pasarow Award in Cancer Research from the Pasarow Foundation, and Le Grand Prix Charles-Leopold Mayer from the Académie des Sciences in France. He also is a co-recipient of the Merck Award from the American Society for Biochemistry and Molecular Biology. Dr. Kornberg is a member of the National Academy of Sciences and a fellow of the American Academy of Arts and Sciences.
Selected Publications : Boeger, H., Bushnell, D.A., avis, R., Griesenbeck, J., Lorch, Y., Strattan, J.S., Westover, K.D., and Kornberg, R.D. (2005) Structural basis of eukaryotic gene transcriptions. FEBS Letters 579:899-903.
Takagi, Y., Masuda, C.A., Chang, W-H, Komori, H., Wang, D., Hunter, T., Joazeiro, C.A.P., and Kornberg, R.D. (2005) Ubiquitin ligase activity of TFIIH and the transcriptional response to DNA damage. Molecular Cell 18:237-243.
Ackerson, C.J., Jadzinsky, P.D., and Kornberg, R.D. (2005) Thiolate ligands for synthesis of water soluble gold clusters. J. Amer. Chem. Soc., in press.
Lorch, Y., Davis, B., and Kornberg, R.D. (2005) Chromatin remodeling by DNA bending, not twisting. Proc. Natll. Acad. Sci. USA 102:1329-1332.
Batada, N., Westover, K.A., Bushnell, D.A., Levitt, M., and Kornberg, R.D. (2004) Diffusion of nucleoside triphosphates and role of the entry site to the RNA polymerase II active center. Proc. Natl. Acad. Sci. USA 101:17361-17364.
Bourbon, H.M. et al. (2004) A unified nomenclature for protein subunits of mediator complexes linking transcriptional regulators to RNA polymerase II. Molecular Cell 14:553-7.
Westover, K.D., Bushnell, D.A., and Kornberg, R.D. (2004) Structural basis of transcription: Nucleotide selection by rotation in the RNA polymerase II active center. Cell 119:481-9.
Boeger, H., Griesenbeck, J., Strattan, J.S., and Kornberg, R.D. (2004) Removal of promoter nucleosomes by disassembly rather than sliding in vivo. Molecular Cell 14:667-673.
Westover, K.D., Bushnell, D.A., and Kornberg, R.D. (2004) Structural basis of transcription: separation of RNA and DNA by RNA polymerase II. Science 303:1014-1016.
Bushnell, D.A., Westover, K.D., Davis, R., and Kornberg, R.D. (2004) Structural basis of transcription: an RNA polymerase II - TFIIB cocrystal at 4.5 Å. Science 303:983-988.
Griesenbeck, J., Boeger, H., Strattan, J.S., and Kornberg. R.D. (2003) Purification of defined chromosomal domains. Methods in Enzymology 375:170-178.
Lorch, Y. and Kornberg, R.D. (2003) Isolation and assay of the RSC chromatin-remodeling complex from Saccharomyces cerevisiae. Methods in Enzymology 377:316-322.
Kuras, L., Borggrefe, T., and Kornberg, R.D. (2003) Association of the Mediator complex with enhancers of active genes. Proc. Natl. Acad. Sci. USA 100:13887-13891.
Takagi, Y., Komori, H., Chang, W.-H., Hudmon, A., Erdjument-Bromage, H., Tempst, P., and Kornberg, R.D. (2003) Revised subunit structure of yeast TFIIH and reconciliation with human TFIIH. J. Biol. Chem. 278:43897-43900.
Griesenbeck, J., Boeger, H., Strattan, J.S., and Kornberg, R.D. (2003) Affinity purification of specific chromatin segments from chromosomal loci in yeast. Mol. Cell. Biol. 23:9275-9282.
Chung, W.-H., Craighead, J.L., Chang, W.-H., Ezeokonkwo, E., Baraket-Samish, A., Kornberg, R.D., and Asturias, F.J. (2003) RNA polymerase II/TFIIF structure and conserved organization of the initiation complex. Molecular Cell 12:1003-1013.
Bushnell, D.A. and Kornberg, R.D. (2003) Complete, 12-subunit RNA polymerase II at 4.1 Å resolution: Implications for the initiation of transcription. Proc. Natl. Acad. Sci. USA 100:6969-6973.
Boeger, H., Griesenbeck, J., and Kornberg, R.D. (2003) Complete unfolding of nucleosomes on a transcriptionally active promoter. Molecular Cell 11:1587-1598.
Asturias, F.J., Chung, W.-C., Kornberg, R.D., and Lorch, Y. (2002) Structural analysis of the RSC chromatin-remodeling complex. Proc. Natl. Acad. Sci. USA 99:13477-13480.
Borggrefe, T., Davis, R., Erdjument-Bromage, H., Tempst, P., and Kornberg, R.D. (2002) A complex of the Srb8, -9, -10, and -11 transcriptional regulatory proteins from yeast. J. Biol. Chem. 277:44202-44207.
Davis, J.A., Takagi, Y. Kornberg, R.D., and Asturias, F.J. (2002) Structure of the yeast RNA polymerase II holoenzyme: conformation and polymerase interaction. Molecular Cell 10:409-415.
Kornberg, R.D. and Lorch Y. (2002) Chromatin structure and transcription: Where do we go from here? Current Opinion in Genetics & Development 12:249-251.
Bushnell, D.A., Cramer, P., and Kornberg, R.D. (2002) Structural basis of transcription: alpha-Amanitin-RNA polymerase II cocrystal at 2.8 Å resolution. Proc. Natl. Acad. Sci. USA 99:1218-1222.
Nagy, P.L., Griesenbeck, J., Kornberg, R.D., and Cleary, M.L. (2002) A truthorax group complex purified from Saccharomyces cerevisiae is required for methylation of histone H3. Proc. Natl. Acad. Sci. USA 99:90-94.
Borggrefe, T., Davis, R., Bareket-Samish, A., and Kornberg, R.D. (2001) Quantitation of the RNA polymerase II transcription machinery in yeast. J. Biol. Chem. 276: 47150-47153.
Kornberg, R.D. (2001) The eukaryotic gene transcription machinery. Biol. Chem. 382:1109-1107.
Li, Y., Takagi, Y., Jiang, Y., Tokunaga, Erdjument-Bromage, H., Tempst, P., and Kornberg, R.D. (2001) A multiprotein complex that interacts with RNA polymerase II elongator. J. Biol. Chem. 276:29628-29631.
Gnatt, A.L., Cramer, P., Fu, J., Bushnell. D.A., and Kornberg, R.D. (2001) Structural basis of transcription: An RNA polymerase II elongation complex at 3.3 Å resolution. Science 292:1876-1882.
Cramer, P., Bushnell, D.A., and Kornberg, R.D. (2001) Structural basis of transcription: RNA polymerase II at 2.8 Ångstrom resolution. Science 292:1863-1876.
Lorch, Y., Zhang, M., and Kornberg, R.D. (2001) RSC unravels the nucleosome. Molecular Cell 7:89-95.
Bushnell, D.A., Cramer, P., and Kornberg, R.D. (2001) Selenomethionine incorporation in Saccharomyces cerevisiae RNA polymerase II. Structure 9:R11-R14.
Dotson, M.R., Yuan, C.X., Roeder, R.G., Myers, L.C., Gustafsson, C.M., Jiang, Y.W., Yang, L., Kornberg, R.D. and Asturias, F.J. (2000) Structural organization of yeast and mammalian mediator complexes. Proc. Natl. Acad. Sci. USA 97:14307-14310.
Chang, W.-H. and Kornberg R.D. (2000) Electron crystal structure of the transcription factor and DNA repair complex, core TFIIH. Cell 102:609-613.
Cramer, P., Bushnell, D.A., Fu, J., Gnatt, A.L., Maier-Davis, B., Thompson, N.E., Burgess, R.R., Edwards, A.M., David, P.R., and Kornberg, R.D. (2000) Architecture of RNA polymerase II and implications for the transcription mechanism. Science 288:640-649.
Feaver, W.J., Huang, W., Gileadi, O., Myers, L., Gustafsson, C.M., Kornberg, R.D., and Friedberg, E.C. (2000) Subunit interactions in yeast transcription/repair factor TFIIH. J. Biol. Chem. 275:5941-5946.
Kornberg, R.D. (1999) Eukaryotic transcriptional control. TIBS 24:M46-M49 (Millennium Issue).
Cairns, B.R., Schlichter, A., Erdjument-Bromage, H., Tempst, P., Kornberg, R.D., and Winston, F. (1999) Two functionally distinct forms of the RSC nucleosome-remodeling complex, containing essential AT hook, BAH, and bromodomains. Molecular Cell 4:715-723.
Fu, J., Gnatt, A.L., Bushnell, D.A., David, P.R., Jensen, G.J., and Kornberg, R.D. (1999) Yeast RNA polymerase II at 5 Å resolution. Cell 98:799-810.
Poglitsch, C.L., Meredith, G., Gnatt, A., Jensen, G.J., Chang, W-H., Fu, J, and Kornberg, R.D. (1999) Electron crystal structure of an RNA polymerase II transcription elongation complex. Cell 98:791-798.
Kornberg, R.D. and Lorch Y. (1999) Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell: 98:285-294.
Kornberg, R.D. and Lorch, Y. (1999) Chromatin-modifying and -remodeling complexes. Current Opinion in Genetics & Development 9:148-151.
Asturias, F.J. and Kornberg, R.D. (1999) Protein crystallization on lipid layers and structure determination of the RNA polymerase II transcription initiation complex. J. Biol. Chem. 274:6813-6816.
Leuther, K.K., Hammarsten, O., Kornberg, R.D., and Chu, G. (1999) Structure of DNA-dependent protein kinase: Implications for its activation by DNA. EMBO J. 18:1114-1123.
Asturias, F.J., Jiang, Y.W., Myers, L.C., Gustafsson, C.M., and Kornberg, R.D. (1999). Conserved structures of Mediator and RNA Polymerase II holoenzyme. Science 283:985-987.
Lorch, Y., Zhang, M., and Kornberg, R.D. (1999) Histone octamer transfer by a chromatin-remodeling complex. Cell 96:389-392.
Myers, L.C., Gustafsson, C.M., Hayashibara, K.C., Brown, P.O., and Kornberg, R.D. (1999) Mediator protein mutations that selectively abolish activated transcription. Proc. Natl. Acad. Sci. USA 96:67-72.
