In their manuscript, Litsios et al. 1 report a new model for how cell growth and biosynthetic activity control the G1/S transition in budding yeast. In essence, Litsios et al. claim that Start is driven by an increasing concentration of the G1 cyclin Cln3 due to a dramatic acceleration of protein synthesis in pre- Start G1 and not by the dilution of the cell cycle inhibitor Whi5. While we previously reported that Start was in part driven by cell growth during G1 diluting out the Start inhibitor Whi5 2 , Litsios et al. report that Whi5 remains at constant concentration during G1, and changes in Whi5 concentration therefore do not contribute to Start . Since Litsios et al. directly contradict several key points of our own model of how cell growth triggers Start , we decided to investigate their claims and data. More specifically, we decided to investigate Litsios et al.’s three major claims: Whi5 concentration remains constant during G1 Cln3 concentration strongly increases prior to Start Global protein synthesis rates increase by 2-3 fold prior to Start We investigated each of these three claims and found that the evidence presented by Litsios et al. does not support their claims due to inadequate analysis methods and flaws in their experiments.

Whi5 is diluted and protein synthesis does not dramatically increase in pre-Start G1