title: Reliable cell cycle commitment in budding yeast is ensured by signal integration.
abstract: Cell fate decisions are critical for life, yet little is known about how their reliability is achieved when signals are noisy and fluctuating with time. In this study, we show that in budding yeast, the decision of cell cycle commitment (Start) is determined by the time integration of its triggering signal Cln3. We further identify the Start repressor, Whi5, as the integrator. The instantaneous kinase activity of Cln3-Cdk1 is recorded over time on the phosphorylated Whi5, and the decision is made only when phosphorylated Whi5 reaches a threshold. Cells adjust the threshold by modulating Whi5 concentration in different nutrient conditions to coordinate growth and division. Our work shows that the strategy of signal integration, which was previously found in decision-making behaviors of animals, is adopted at the cellular level to reduce noise and minimize uncertainty.
authors.affiliation: Center for Quantitative Biology, Peking University, Beijing, China.
authors.forename: Xili
authors.initials: X
authors.lastname: Liu
authors.affiliation: Center for Quantitative Biology, Peking University, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Center for Quantitative Biology, Peking University, Beijing, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Yang
authors.affiliation: Institute of Molecular Biology, College of Medical Science, China Three Gorges University, Yichang, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Liu
authors.affiliation: Center for Quantitative Biology, Peking University, Beijing, China.
authors.forename: Lingli
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Center for Quantitative Biology, Peking University, Beijing, China.
authors.forename: Yimiao
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Center for Quantitative Biology, Peking University, Beijing, China.
authors.forename: Lufeng
authors.initials: L
authors.lastname: Hu
authors.affiliation: Center for Quantitative Biology, Peking University, Beijing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Ouyang
authors.affiliation: Center for Quantitative Biology, Peking University, Beijing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Tang
mesh_terms: D002453:Cell Cycle; D016193:G1 Phase; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D004718:Saccharomycetales / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D029701:Saccharomyces cerevisiae Proteins
keywords: Cln3 integration; S. cerevisiae; Whi5 phosphorylation; cell biology; cell cycle; cell decision-making; cell size control