芽殖酵母S期检验点通路定量生物学研究

Quantitative Study of S-Phase Checkpoint Pathway in Budding Yeast

构建由羟基脲(HU)诱导的芽殖酵母S期检验点激活和调控DNA复制的理论模型。模拟结果表明,对于不同浓度HU的刺激,检验点激活和调控系统的反应存在霍普夫分岔,其中的分岔点对应于检验点激活的HU阈值浓度;而且发现该通路的激活过程在较大参数范围内会出现振荡现象。同时,利用构建了Rnr3-GFP荧光蛋白的酵母菌株,在不同的HU浓度刺激下,测量酵母菌Rnr3蛋白多时间点的表达水平,得到酵母菌对HU浓度的实验反应阈值,与理论结果相符合。这一工作构建了酵母S期检验点定量研究的基本框架,可为进一步的理论和实验研究提供线索。

The authors construct an ODE model for S-phase checkpoint activation and its regulation of DNA replication induced by hydroxyurea（HU） in budding yeast. The simulation result shows that the checkpoint response system behaves Hopf bifurcation to different concentration of HU stress, and the bifurcation corresponds to the threshold of the checkpoint activation, and predicts that there might appear oscillation phenomena in the pathway. Further, the threshold in the budding yeast strain containing Rnr3-GFP fluorescence reporter is observed in experiment. This work establishes basic framework for the yeast S-phase checkpoint activation, and provides clue for future experimental work.