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SUBUNIT INTERACTIONS OF COMPONENTS OF YEAST PAF1 COMPLEX

Award Number: R15GM076099
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2006
PERIOD OF PERFORMANCE END DATE: 12/31/2010

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SUBUNIT INTERACTIONS OF COMPONENTS OF YEAST PAF1 COMPLEX - DESCRIPTION (provided by applicant): Regulation of mRNA synthesis by RNA polymerase II (pol II) is critical for proper development, homeostasis and functioning of organisms; misregulation contributes to serious diseases including cancer. Pol II is a scaffold upon which other factors important for transcription and post-transcriptional processing of mRNAs assemble, including the general transcription factors, TATA-binding protein and its associated factors, the Mediator complex, the capping enzyme complex and the cleavage/polyadenylation factors. In addition to these factors, the Paf1 complex (Paf1C), associated with pol II at the promoter and in coding regions of genes, is emerging as an important player orchestrating the binding and activity of transcription and post- transcriptional factors. Containing Paf1, Ctr9, Rtf1, Leo1 and Cdc73, the yeast Paf1C is now linked genetically and physically to initiation and elongation factors and to post-transcriptional processing of mRNA. Mutation of yeast Paf1 factors Is not lethal, but causes severe, pleiotropic phenotypes, and results in changes in polyadenylation and the abundance of a subset of mRNAs. Mutation of the human Cdc73 homolog (parafibromin) results in human parathyroid and jaw tumors defining the Paf1C as a human tumor suppressor. We still do not know the interconnections of the Paf1C components or how the complex associates with pol II. Nor do we have a definition of the direct protein/protein contacts made with other transcription and RNA processing factors. Two genome scale analyses of yeast protein-protein interactions have not identified any of these interactions, due in part to failure to include the correct coding regions for the Paf1C factors in the screens. This project proposes a directed test of protein-protein interactions of the members of the Paf1C, with each other, with pol II subunits, and with other functionally linked factors. The yeast two-hybrid technique will be used to detect interactions of proteins in vivo. A complementary in vitro approach will use yeast strains with pairs of tagged proteins to look for co-immunoprecipitation of proteins in both wild-type and Paf1C factor mutant yeast strains. Our results will build a model of the organization of the yeast Paf1C and its interactions critical for understanding how this important complex functions as a tumor suppressor in humans. The simplicity of the model system and techniques to be used assure that under- graduates will be able to make significant contributions to the important questions asked in this proposal.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2010 ( Subtotal = $0 )
2010	2006	REGIS UNIVERSITY	3333 REGIS BOULEVARD	DENVER	CO	80221	ADAMS	USA	Biomedical Research and Research Training	000	1	10/29/2009	NEW	$0
														Subtotal = $0

Issue Date FY: 2006 ( Subtotal = $188,502 )
2006	2006	REGIS UNIVERSITY	3333 REGIS BOULEVARD	DENVER	CO	80221	ADAMS	USA	Biomedical Research and Research Training	000	1	12/9/2005	NEW	$188,502
														Subtotal = $188,502

Grand Total All Awards = $188,502

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SUBUNIT INTERACTIONS OF COMPONENTS OF YEAST PAF1 COMPLEX

Award Number: R15GM076099

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/01/2006

PERIOD OF PERFORMANCE END DATE: 12/31/2010

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