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.

中文翻译：

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G1 蛋白产生和细胞大小动力学之间的差异缩放促进了出芽酵母细胞分裂周期的承诺。

在单细胞真核生物酿酒酵母中，Cln3 细胞周期蛋白依赖性激酶活性启用 Start，即对细胞分裂周期的不可逆承诺。然而，自相矛盾地认为，Cln3 的浓度在 G1 期间保持不变，因为假定其生产率随细胞大小动态而缩放。测量单个细胞在细胞周期进程中的代谢和生物合成活性，我们发现细胞在其蛋白质产生速率中表现出脉冲。这些脉冲不是随着细胞大小动态而缩放，而是遵循内在的代谢动态，在 Start 附近达到峰值。使用基于病毒的双顺反子结构和靶向蛋白质组学在单细胞和群体水平上测量 Cln3，我们表明，蛋白质产量和细胞大小之间的差异缩放导致 Cln3 浓度的时间增加，并通过 Start。这种不同的缩放比例导致子细胞和母细胞在生长条件下都开始。因此，两个基本生理参数之间的解偶联驱动细胞周期承诺。