Our long-term goal is to understand the structural basis for the regulation of RNA polymerase II Imachinery in the transcription cycle. The eukaryotic mRNA synthesis system has emerged as an enormous protein apparatus consisting of RNA polymerase II (Pol II) at its heart surrounded by layers of controlling factors. We recently cracked the phase problem for the 10-subunit Pol II (500 kDa) from yeast. This advent has made it feasible to unveil the apparatus in a more elaborate fashion, so we can analyze Pol II-factor(s) interactions that modulate the transcription activities of Pol I1. Transcription is the first step in gene expression. Signals from many cellular processes such as nutrient sensing, catabolite repression, hormone stimulation, differentiation and responses to environmental stimuli ultimately reach the level of transcription to exert their effects. Aberration of transcriptional control is one of the mechanisms underlying tumorigenesis, since cancer arises from disruption of the fine balance between proliferative and differentiative genetic programs. Oncogene products are frequently found to be key players in the control networks of signal transduction, cell cycle and transcription regulations. We propose to examine, in yeast, various Pol II-factor(s) complexes corresponding to distinct functional steps in the transcription cycle. Biochemical and X-ray crystallographic methods developed in the work of the 10-subunit Pol II and the ribosome will be employed, refined and extended to tackle this new generation of structural problems in transcription regulation.
Specific aims for the project period are crystal structure determinations of three Pol II-factor complexes, including the pre-mRNA 5' capping enzyme, a Pol II specific phosphatase Fcpl and a subassembly of the Pol II transcription preinitiation complex. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM064651-05
Application #
7149157
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Program Officer
Tompkins, Laurie
Project Start
2002-09-01
Project End
2007-08-31
Budget Start
2006-12-01
Budget End
2007-08-31
Support Year
5
Fiscal Year
2007
Total Cost
$291,652
Indirect Cost
Name
Cornell University
Department
Biochemistry
Type
Schools of Earth Sciences/Natur
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
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