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

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.

journal_name

Nat Cell Biol

journal_title

Nature cell biology

authors

Litsios A,Huberts DHEW,Terpstra HM,Guerra P,Schmidt A,Buczak K,Papagiannakis A,Rovetta M,Hekelaar J,Hubmann G,Exterkate M,Milias-Argeitis A,Heinemann M

doi

10.1038/s41556-019-0413-3

subject

Has Abstract

pub_date

2019-11-01 00:00:00

pages

1382-1392

issue

11

eissn

1465-7392

issn

1476-4679

pii

10.1038/s41556-019-0413-3

journal_volume

21

pub_type

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