Absolute protein quantitation reveals a nutrient-dependent link between cell growth and division

Abstract

How a cell knows when it has grown large enough to divide is a fundamental unanswered question with broad implications to understanding disease. Cell size homeostasis, or the balance between growth and division, is modulated by growth factors in mammalian cells and by nutrients in the model organism, budding yeast, such that cells grown in rich nutrients are larger than those grown in poor nutrients. Although decades of investigation and hundreds of papers have been put forth seeking to uncover the missing link between the distinctly regulated processes of growth and division, progress has been hampered by genetic complexity and an overwhelming amount of qualitative data , lacking complementary reproducible quantitative data. Implementing a particle-counting fluorescence-fluctuation technique in live single yeast cells in respect to cell growth and time, we determined absolute quantification of key proteins regulating the commitment to cell division at the G1/S cell cycle transition, termed Start. We found the number of G1/S transcription factors is growth and nutrient dependent, and the ratio of transcription factors to number of promoter sites of the G1/S regulon is a key determinant of Start. This work explains in part how cell growth and extracellular nutrient conditions dictate at what size a single yeast cell commits to divide.