Differential scaling between G1 protein production and cell size dynamics promotes commitment to the cell division cycle in budding yeast

Athanasios Litsios, Daphne H E W Huberts, Hanna M Terpstra, Paolo Guerra, Alexander Schmidt, Katarzyna Buczak, Alexandros Papagiannakis, Mattia Rovetta, Johan Hekelaar, Georg Hubmann, Marten Exterkate, Andreas Milias-Argeitis*, Matthias Heinemann

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)
185 Downloads (Pure)

Abstract

In the unicellular eukaryote Saccharomyces cerevisiae, Cln3-cyclin-dependent kinase activity enables Start, the irreversible commitment to the cell division cycle. However, the concentration of Cln3 has been paradoxically considered to remain constant during G1, due to the presumed scaling of its production rate with cell size dynamics. Measuring metabolic and biosynthetic activity during cell cycle progression in single cells, we found that cells exhibit pulses in their protein production rate. Rather than scaling with cell size dynamics, these pulses follow the intrinsic metabolic dynamics, peaking around Start. Using a viral-based bicistronic construct and targeted proteomics to measure Cln3 at the single-cell and population levels, we show that the differential scaling between protein production and cell size leads to a temporal increase in Cln3 concentration, and passage through Start. This differential scaling causes Start in both daughter and mother cells across growth conditions. Thus, uncoupling between two fundamental physiological parameters drives cell cycle commitment.

Original languageEnglish
Pages (from-to)1382-1392
Number of pages11
JournalNature Cell Biology
Volume21
Issue number11
DOIs
Publication statusPublished - 4-Nov-2019

Keywords

  • SACCHAROMYCES-CEREVISIAE
  • GLYCOLYTIC OSCILLATIONS
  • METABOLIC CYCLE
  • GROWTH
  • CLN3
  • TRANSCRIPTION
  • ACCURACY
  • GLUCOSE
  • GENE
  • MASS

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