Cell Cycle Regulation by Nutrient Signals in S. cerevisiae

University Of Wisconsin-Madison, Madison WI

Investigators

Abstract

Although yeast grow well on a variety of carbon sources, different nutrients produce widely differing growth rates. In order for the cells to maintain the proper size at these different growth rates, they must adjust their rate of progress through the cell division cycle to match the rate at which they accumulate size. These changes in cell cycle length can be largely accounted for as changes in the length of time spent in G1. Although progress through G1 is thought to be regulated by the products of the CLN3 and BCK2 genes, how these genes actually regulate the timing of the G1 to S phase transition is unclear. Preliminary results show that glucose regulates translation of Cln3 through the Ras/cAMP signaling pathway, and that glucose also regulates transcription of CLN3 through a set of repeated elements in the CLN3 promoter. These repeats drive glucose dependent expression of reporter genes, and are necessary for proper glucose regulation of CLN3 mRNA and protein levels. The repeated elements also bind at least one protein from yeast extracts, and are found upstream of a large group of genes that are also regulated by glucose. The hypothesis is that Cln3 regulates the length of time that cells spend in G1, allowing cells to adjust the cell cycle length to match the rate of physical growth in size, will be tested, and the mechanism by which glucose regulates CLN3 transcription will be determined. The specific goals of the project are to determine the role that CLN3 expression plays in maintaining cell size, to identify genes that regulate transcription of CLN3 in response to glucose, and to determine how the products of these genes function. The results of these experiments will reveal the links between glucose metabolism, G1 cyclin expression, progress through the cell cycle, and maintenance of constant cell size in yeast. Because the glucose responsive elements in the CLN3 promoter are also found upstream of a large number of glucose sensitive yeast genes, glucose regulation of CLN3 transcription may be part of a process that regulates a large number of genes in a coordinated fashion.