| Title: | When yeast cells change their mind: cell cycle 'Start' is reversible under starvation |
| Author(s): | Irvali D; Schlottmann FP; Muralidhara P; Nadelson I; Kleemann K; Wood NE; Doncic A; Ewald JC; |
| Address: | "Interfaculty Institute of Cell Biology, University of Tuebingen, Tuebingen, Germany. The University of Texas Southwestern Medical Center, Dallas, TX, USA" |
| ISSN/ISBN: | 1460-2075 (Electronic) 0261-4189 (Print) 0261-4189 (Linking) |
| Abstract: | "Eukaryotic cells decide in late G1 phase of the cell cycle whether to commit to another round of division. This point of cell cycle commitment is termed 'Restriction Point' in mammals and 'Start' in the budding yeast Saccharomyces cerevisiae. At Start, yeast cells integrate multiple signals such as pheromones and nutrients, and will not pass Start if nutrients are lacking. However, how cells respond to nutrient depletion after the Start decision remains poorly understood. Here, we analyze how post-Start cells respond to nutrient depletion, by monitoring Whi5, the cell cycle inhibitor whose export from the nucleus determines Start. Surprisingly, we find that cells that have passed Start can re-import Whi5 into the nucleus. In these cells, the positive feedback loop activating G1/S transcription is interrupted, and the Whi5 repressor re-binds DNA. Cells which re-import Whi5 become again sensitive to mating pheromone, like pre-Start cells, and CDK activation can occur a second time upon replenishment of nutrients. These results demonstrate that upon starvation, the commitment decision at Start can be reversed. We therefore propose that cell cycle commitment in yeast is a multi-step process, similar to what has been suggested for mammalian cells" |
| Keywords: | Saccharomyces cerevisiae/metabolism *Saccharomyces cerevisiae Proteins/genetics/metabolism Cell Cycle Cell Division G1 Phase *Saccharomycetales/metabolism Saccharomyces cerevisiae cell division cycle metabolism nutrient signaling quiescence; |
| Notes: | "MedlineIrvali, Deniz Schlottmann, Fabian P Muralidhara, Prathibha Nadelson, Iliya Kleemann, Katja Wood, N Ezgi Doncic, Andreas Ewald, Jennifer C eng Research Support, Non-U.S. Gov't England 2022/11/25 EMBO J. 2023 Jan 16; 42(2):e110321. doi: 10.15252/embj.2021110321. Epub 2022 Nov 23" |
