REGULATION OF CELL-SIZE BY GLUCOSE IS EXERTED VIA REPRESSION OF THE CLN1 PROMOTER

Yeast cells are keenly sensitive to the availability and quality of nu trients. Addition of glucose to cells growing on a poorer carbon sourc e elicits a cell cycle delay during G(1) phase and a concomitant incre ase in the cell size. The signal is transduced through the RAS-cyclic AMP pathway. Using synchronized populations of G(1) cells, we show tha t the increase in cell size required for budding depends upon CLN1 but not other G(1) cyclins. This delay in cell cycle initiation is associ ated specifically with transcriptional repression of CLN1. CLN2 is not repressed. Repression of CLN1 is not limited to the first cycle follo wing glucose addition but occurs in each cell cycle during growth on g lucose. A 106-bp fragment of the CLN1 promoter containing the three Ml uI cell cycle box (MCB) core elements responsible for the majority of CLN1-associated upstream activation sequence activity is sufficient to confer glucose-induced repression on a heterologous reporter. A mutan t CLN2 promoter that is rendered dependent upon its three MCB core ele ments due to inactivation of its Swi4-dependent cell cycle box (SCB) e lements is also repressed by glucose. The response to glucose is parti ally suppressed by inactivation of SWI4, but not MBP1, which is consis tent with the dependence of MCB core elements upon the SCB-bindigg tra nscription factor (SBF). We suggest that differential regulation of CL N1 and CLN2 by glucose results from differences in the capacity of SBF to activate transcription driven by SCB and MCB core elements. Finall y, we show that transcriptional repression is sufficient to explain th e cell cycle delay that occurs in response to glucose.