Nutritional cell cycle reprogramming reveals that inhibition of Cdk1 is required for proper MBF-dependent transcription

Abstract

In Nature, cells and in particular unicellular microorganisms are exposed to a variety of nutritional environments. Fission yeast cells cultured in nitrogen-rich media grow fast, divide with a large size and show a short G1 and a long G2. However, when they are cultured in nitrogen-poor media they reduce the growth rate and cell size and show a long G1 and a short G2. In this study, we have compared the phenotypes of cells lacking the highly conserved Cdk inhibitor Rum1 and the APC/C activator Ste9 in nitrogen-rich and nitrogen-poor media. Rum1 and Ste9 are dispensable for cell division in nitrogen-rich medium. However, in nitrogen-poor medium they are essential to generate a proper wave of MBF-dependent transcription at the end of G1, which is critical to promote a successful S-phase. Mutants lacking Rum1 and Ste9 showed premature entry into S-phase and a reduced wave of MBF-dependent transcription, leading to replication stress, DNA damage and G2 cell cycle arrest. In conclusion, this work demonstrates how reprogramming the cell cycle by the nutritional environment may reveal new roles of cell cycle regulators.