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 …

Cells have to make reliable decisions in response to external and/or internal signals that can
be noisy and varying. For budding yeast Saccharomyces cerevisiae, cells decide whether
and when to commit to cell division at the Start checkpoint. The decision is irreversible and
has the physiological significance for coordinating cell growth with cell division. The trigger
of the Start, the G1 cyclin Cln3 is a dynamic sensor of the nutrient and cellular conditions
with low copy number and rapid turnover time. Here we quantitatively investigate how cells …