Forced periodic expression of G1 cyclins phase-locks the budding yeast cell cycle
Forced periodic expression of G1 cyclins phase-locks the budding yeast cell cycle
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DOI：
10.1073/pnas.0809227106
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发表时间：
2009-04-21
影响因子：
11.1
通讯作者：
Siggia, E. D.
中科院分区：
文献类型：
--
作者：
Charvin, G.;Cross, F. R.;Siggia, E. D.
振荡器的锁相（频率夹带）是研究振荡器稳定性和结构的有用特性，其中周期性外部信号以不同于未扰动频率的频率驱动振荡。细胞周期经常被描述为生化振荡器;然而，由于这种振荡器与关键的生物学事件（如DNA复制和分离）以及细胞生长（细胞质量增加）有关，因此尚不清楚细胞周期振荡器是否可能锁相。我们发现，强制周期性表达的G（1）细胞周期蛋白CLN 2期锁定了芽殖酵母细胞周期的一系列外在时期在一个指数增长的单层培养。我们使用返回图来确定外部控制脉冲的夹带效率，从而确定谱系中细胞的行为。我们量化母亲和女儿之间的差异，以及如何扩大人口同步不同的同步一个振荡器。母亲只是间歇性锁定，而女儿完全锁定，并在不同的时期范围比母亲。我们可以用一个基于细胞大小控制和质量如何在母细胞和子细胞之间分配的可解析模型来解释这两种细胞类型中锁相的定量特征。该模型的一个关键预测是，大小控制不仅可以发生在G（1）中，而且在适当的条件下也可以发生在细胞周期的后期;我们的实验数据证实了这一预测。我们的研究结果提供了定量的洞察细胞大小是如何与细胞周期振荡器集成。
Phase-locking (frequency entrainment) of an oscillator, in which a periodic extrinsic signal drives oscillations at a frequency different from the unperturbed frequency, is a useful property for study of oscillator stability and structure. The cell cycle is frequently described as a biochemical oscillator; however, because this oscillator is tied to key biological events such as DNA replication and segregation, and to cell growth (cell mass increase), it is unclear whether phase locking is possible for the cell cycle oscillator. We found that forced periodic expression of the G(1) cyclin CLN2 phase locks the cell cycle of budding yeast over a range of extrinsic periods in an exponentially growing monolayer culture. Wecharacterize the behavior of cells in a pedigree using a return map to determine the efficiency of entrainment to the externally controlled pulse. We quantify differences between mothers and daughters and how synchronization of an expanding population differs from synchronization of a single oscillator. Mothers only lock intermittently whereas daughters lock completely and in a different period range than mothers. We can explain quantitative features of phase locking in both cell types with an analytically solvable model based on cell size control and how mass is partitioned between mother and daughter cells. A key prediction of this model is that size control can occur not only in G(1), but also later in the cell cycle under the appropriate conditions; this prediction is confirmed in our experimental data. Our results provide quantitative insight into how cell size is integrated with the cell cycle oscillator.