Transcription by RNA Polymerase II is the mechanism by which all mRNA is generated. Transcription is responsible for reading the genome and is key in regulation of the cell. It is also aberrant in cancer cells. Our goal is to understand the complex mechanisms involved in transcription and utilize that information to develop novel therapeutics for cancer treatment. There are three main avenues by which we are invested to reach our goal.
1) Biochemical analysis of key components in the transcription apparatus: We have discovered a new RNA Polymerase II subunit with a crucial cellular function.
2) Structural analysis of the transcription machinery: We have purified large amounts of mammalian RNA Polymerase II for structural determination.
3) Disclosure of Transcription Factor targets for cancer therapy and drug development: We have disclosed a key transcription factor, which has potential as a cancer target and continue to develop therapeutic strategies for the new target.
Lab Techniques and Equipment
We employ a broad range of techniques. It is our belief that research is the goal and that any technique needed to achieve an understanding of the problem will be performed. As such we use molecular biology (DNA/RNA work, genearray technology, PCR etc.), biochemistry (protein purification, biochemical assays etc) and x-ray crystallography (to determine the structure of key components in the transcription apparatus).
• Bar-Ilan University, Ramat-Gan, Israel, BSc.,1980-1984,Biology
• Weizmann Institute of Science, Rehovot, Israel, MSc.,1984-1986,Neurobiology
• Hebrew University of Jerusalem, Givat-Ram, Israel, PhD,1986-1991,Biochemistry
• Stanford University, Stanford, California ,Postdoc,1992-1999,Structural Biology
• Hu, X., Malik, S., Negroiu, C.C., Hubbard, K., Velalar CN., Hampton B., Grosu D., Catalano, J., Roeder, R.G., and Gnatt, A. (2006) A Mediator-responsive form of metazoan RNA polymerase II. Proc. Natl. Acad. Sci. USA. 103:9506-11
• Suh MH, Ye P, Zhang M, Hausmann S, Shuman S, Gnatt AL, Fu J. (2005) Fcp1 directly recognizes the C-terminal domain (CTD) and interacts with a site on RNA polymerase II distinct from the CTD. Proc. Natl. Acad. Sci. USA. 102:17314-9.
• Gnatt, A., Cramer, P., Fu, J., Bushnell, D., and Kornberg, R. (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., 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 288:640-9.
• Fu, J., Gnatt, A., Bushnell, D., Jensen, G.J., Thompson, N.E., Burgess, R.T., David, P., and Kornberg, R.D (1999). Yeast RNA polymerase II at 5 Resolution. Cell 98:799-810.
• Fu, J., Gerstein, M., David, P., Gnatt, A., Bushnell, D., Edwards, A.M., and Kornberg, R.D., (1998) Repeated tertiary fold of RNA polymerase II and implications for DNA Binding. J.Mol. Biol. 280:317-32.
• Gnatt, A., Cramer, P., Fu, J., Bushnell, D., and Kornberg, R., (2001) Structural basis of transcription: an RNA Polymerase II elongation complex at 3.3 Resolution. Science (accepted for publication in June).
• Gnatt, A., Fu, J. and Kornberg, R.D. (1997) Formation and crystallization of yeast RNA polymerase II elongation complexes. J. of Biol. Chem. 272:30799-30805.
• Poglitsch, C.L., Meredith, G.D., Gnatt, A., Jensen, G.J., Chang, W., Fu, J., and Kornberg R. (1999). Electron crystal structure of an RNA polymerase II transcription elongation complex. Cell 98:791-798.
• Svejstrup, Q. J., Li, Y., Fellows, J., Gnatt, A., Bjorklund, S., and Kornberg, R.D. (1997) Evidence for a mediator cycle at the initiation of transcription. Proc. Natl. Acad. Sci. USA 94:6075-6078.