Li Shenghua, Brazhnik Paul, Sobral Bruno, Tyson John J
Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America.
PLoS Comput Biol. 2008 Jan;4(1):e9. doi: 10.1371/journal.pcbi.0040009. Epub 2007 Dec 5.
Progression of a cell through the division cycle is tightly controlled at different steps to ensure the integrity of genome replication and partitioning to daughter cells. From published experimental evidence, we propose a molecular mechanism for control of the cell division cycle in Caulobacter crescentus. The mechanism, which is based on the synthesis and degradation of three "master regulator" proteins (CtrA, GcrA, and DnaA), is converted into a quantitative model, in order to study the temporal dynamics of these and other cell cycle proteins. The model accounts for important details of the physiology, biochemistry, and genetics of cell cycle control in stalked C. crescentus cell. It reproduces protein time courses in wild-type cells, mimics correctly the phenotypes of many mutant strains, and predicts the phenotypes of currently uncharacterized mutants. Since many of the proteins involved in regulating the cell cycle of C. crescentus are conserved among many genera of alpha-proteobacteria, the proposed mechanism may be applicable to other species of importance in agriculture and medicine.
细胞通过分裂周期的进程在不同步骤受到严格控制,以确保基因组复制的完整性以及向子细胞的分配。基于已发表的实验证据,我们提出了一种新月柄杆菌细胞分裂周期控制的分子机制。该机制基于三种“主调控因子”蛋白(CtrA、GcrA和DnaA)的合成与降解,被转化为一个定量模型,以研究这些及其他细胞周期蛋白的时间动态。该模型考虑了柄状新月柄杆菌细胞周期控制在生理学、生物化学和遗传学方面的重要细节。它再现了野生型细胞中的蛋白质时间进程,正确模拟了许多突变菌株的表型,并预测了目前未表征突变体的表型。由于参与调控新月柄杆菌细胞周期的许多蛋白质在α-变形菌的许多属中是保守的,因此所提出的机制可能适用于农业和医学中其他重要的物种。