Growth-dependent signals drive an increase in early G1 cyclin concentration to link cell cycle entry with cell growth.

Robert A Sommer,Jerry T Dewitt,Douglas R Kellogg,Raymond Tan

doi:10.7554/elife.64364

Abstract

Entry into the cell cycle occurs only when sufficient growth has occurred. In budding yeast, the cyclin Cln3 is thought to initiate cell cycle entry by inactivating a transcriptional repressor called Whi5. Growth-dependent changes in the concentrations of Cln3 or Whi5 have been proposed to link cell cycle entry to cell growth. However, there are conflicting reports regarding the behavior and roles of Cln3 and Whi5. Here, we found no evidence that changes in the concentration of Whi5 play a major role in controlling cell cycle entry. Rather, the data suggest that cell growth triggers cell cycle entry by driving an increase in the concentration of Cln3. We further found that accumulation of Cln3 is dependent upon homologs of mammalian SGK kinases that control cell growth and size. Together, the data are consistent with models in which Cln3 is a crucial link between cell growth and the cell cycle.

Highlights

Cell cycle progression is subservient to cell growth
The isolated cells were resuspended in YP media containing rich carbon (2% dextrose) or poor carbon to initiate growth in G1 phase
Another advantage is that the cells shifted to rich carbon undergo a prolonged interval of growth in G1 phase to reach the increased size that is characteristic of cells growing in rich carbon, which provides a longer interval for examining the behavior of Cln3 and Whi5

Summary

Introduction

Cell cycle progression is subservient to cell growth. key cell cycle transitions occur only when sufficient growth has occurred. Most models suggest that growth-dependent changes in the number or concentration of key cell cycle regulatory proteins trigger cell cycle entry. If the number of molecules of a protein increases at the same rate as growth, the number of molecules per cell will increase but the concentration of the protein will stay constant. Cell cycle entry could require changes in the concentration of cell cycle regulatory proteins In this case, if the number of molecules per cell increases faster than growth, the concentration and activity of the protein should increase. If the number of protein molecules stays constant as growth occurs the concentration of the molecule will decrease It remains unclear whether changes in number or concentration of cell cycle regulators triggers cell cycle entry. It remains possible that changes in the catalytic rate of an enzyme, such as a kinase or phosphatase, play an important role

Methods

Results

Conclusion