Kinetic Analysis of a Molecular Model of the Budding Yeast Cell Cycle

TLDR

The cell‑cycle machinery of budding yeast is well characterized, with cyclins Cln1–3 and Clb1–6 orchestrating DNA synthesis, bud emergence, spindle formation, nuclear division, and cell separation, and experimental evidence pointing to a mechanistic framework for cyclin synthesis and degradation. We translate this mechanistic framework into differential equations that model the time courses of three major cyclin‑dependent kinase activities and use the model to analyze the Start and Finish checkpoints in wild‑type cells and 50 mutants. The resulting model reproduces key physiological, biochemical, and genetic observations of budding‑yeast cell‑cycle control.

Abstract

The molecular machinery of cell cycle control is known in more detail for budding yeast, Saccharomyces cerevisiae, than for any other eukaryotic organism. In recent years, many elegant experiments on budding yeast have dissected the roles of cyclin molecules (Cln1–3 and Clb1–6) in coordinating the events of DNA synthesis, bud emergence, spindle formation, nuclear division, and cell separation. These experimental clues suggest a mechanism for the principal molecular interactions controlling cyclin synthesis and degradation. Using standard techniques of biochemical kinetics, we convert the mechanism into a set of differential equations, which describe the time courses of three major classes of cyclin-dependent kinase activities. Model in hand, we examine the molecular events controlling “Start” (the commitment step to a new round of chromosome replication, bud formation, and mitosis) and “Finish” (the transition from metaphase to anaphase, when sister chromatids are pulled apart and the bud separates from the mother cell) in wild-type cells and 50 mutants. The model accounts for many details of the physiology, biochemistry, and genetics of cell cycle control in budding yeast.