This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 Fcp1 and a subassembly of the Pol II transcription preinitiation complex.
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