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Originally published as Genetics Published Articles Ahead of Print on December 15, 2005.

Genetics, Vol. 172, 1459-1476, March 2006, Copyright © 2006
doi:10.1534/genetics.105.053041

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Genomewide Screen Reveals a Wide Regulatory Network for Di/Tripeptide Utilization in Saccharomyces cerevisiae

Houjian Cai*, Sarah Kauffman*, Fred Naider{dagger} and Jeffrey M. Becker*,1

* Department of Microbiology, University of Tennessee, Knoxville, Tennessee 37996-0845 and {dagger} Department of Chemistry and Macromolecular Assemblies Institute, Graduate School and University Center, College of Staten Island, CUNY, New York, New York 10314

1 Corresponding author: Department of Microbiology, University of Tennessee, M409 Walters Bldg., Knoxville, TN 37996-0845.
E-mail: jbecker{at}utk.edu

Small peptides of two to six residues serve as important sources of amino acids and nitrogen required for growth by a variety of organisms. In the yeast Saccharomyces cerevisiae, the membrane transport protein Ptr2p, encoded by PTR2, mediates the uptake of di/tripeptides. To identify genes involved in regulation of dipeptide utilization, we performed a systematic, functional examination of this process in a haploid, nonessential, single-gene deletion mutant library. We have identified 103 candidate genes: 57 genes whose deletion decreased dipeptide utilization and 46 genes whose deletion enhanced dipeptide utilization. On the basis of Ptr2p-GFP expression studies, together with PTR2 expression analysis and dipeptide uptake assays, 42 genes were ascribed to the regulation of PTR2 expression, 37 genes were involved in Ptr2p localization, and 24 genes did not apparently affect Ptr2p-GFP expression or localization. The 103 genes regulating dipeptide utilization were distributed among most of the Gene Ontology functional categories, indicating a very wide regulatory network involved in transport and utilization of dipeptides in yeast. It is anticipated that further characterization of how these genes affect peptide utilization should add new insights into the global mechanisms of regulation of transport systems in general and peptide utilization in particular.




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