Control of the yeast cell cycle with a photocleavable alpha-factor analogue.

Abstract

The budding yeast Saccharomyces cerevisiae is widely used as a model organism for studying many biological processes and systems, particularly for understanding the cell cycle. The yeast peptide pheromone α-factor (WHWLQLKPGQPMY) activates the mating pathway in MATa cells, arresting the cell cycle in the G1 phase. This arrest is used as a tool for synchronizing yeast cultures and for investigating signaling events involved in the pathway and other processes related to morphogenesis and transcription. Herein we report the synthesis and activity of an α-factor analogue designed to control the on/off state of the mating signal. Incorporating a photocleavable residue at a flexible site in the peptide allowed UV degradation in situ to mimic the natural protease degradation of this signaling peptide. The control over the α-factor signal achieved serves as proof of concept for use of this analogue as a tool. It also and allows access to previously impractical experiments that will yield highly time-resolved information about the yeast cell cycle and mating pathway.