Title

The global transcriptional activators Gcr1 and Gcr2 mediate the response to glucose and stimulate cell cycle progression through M/G1

Date of Award

2003

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biological Sciences

First Advisor

George Santangelo

Advisor Department

Biological Sciences

Abstract

The budding yeast Saccharomyces cerevisiae is an excellent model system to study eukaryotic regulatory networks that control the proliferative response to nutrients; in higher eukaryotes, this response is linked both to normal developmental processes and to the mechanism of diseases such as cancer. In both multicellular eukaryotes and in yeasts, growth requires coordination of cell cycle events, such as DNA duplication and new cell wall deposition, with constitutive functions like energy generation and duplication of protein mass. In yeast cells, the latter two processes are stimulated by the phosphoprotein Gcr1p, a transcriptional activator of glycolytic and ribosomal protein genes. Gcr2p, another S. cerevisiae activator with homology to Gcr1p, is required for hyperphosphorylation of Gcr1p and mediates the specialized mechanism of Gcr1p activation. I show here that the two Gcr1p-controlled cellular responses to glucose provide regulatory input into cell cycle progression. This work also demonstrates that the gcr1Δ mutant itself has a cell cycle phenotype. Further, genetic interactions with known cell cycle regulators suggest that Gcr1p and Gcr2p represent a regulatory nexus for the coordination of cell cycle progression and growth.