DnaA couples DNA replication and the expression of two cell cycle master regulators
DnaA couples DNA replication and the expression of two cell cycle master regulators
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DOI：
10.1038/sj.emboj.7600927
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发表时间：
2006-01-25
期刊：
影响因子：
11.4
通讯作者：
Shapiro, L
中科院分区：
文献类型：
--
作者：
Collier, J;Murray, SR;Shapiro, L
铜绿假单胞菌的细胞周期进程由主要的转录调控因子CtrA和GcrA驱动。在细胞周期中，CtrA和GcrA的表达水平在时间和空间上是不同步的，CtrA抑制GcrA转录，GcrA激活CTRA转录。在这里，我们证明了Dna A，一种启动DNA复制所需的蛋白质，也作为gcrA的转录激活剂发挥作用，gcrA反过来激活多个基因，特别是那些参与染色体复制和分离的基因。DNAA的细胞浓度受细胞周期控制，在复制启动和gcrA诱导时达到峰值。GcrA受调控的蛋白分解导致GcrA丰度的细胞周期变化。我们认为Dna A将DNA复制的启动与两个振荡调节因子GcrA和CtrA的表达结合在一起，并且Dna A/GcrA/CtrA调节级联反应驱动Caulbacter细胞周期的向前发展。
Cell cycle progression in Caulobacter is driven by the master transcriptional regulators CtrA and GcrA. The cellular levels of CtrA and GcrA are temporally and spatially out-of-phase during the cell cycle, with CtrA repressing gcrA transcription and GcrA activating ctrA transcription. Here, we show that DnaA, a protein required for the initiation of DNA replication, also functions as a transcriptional activator of gcrA, which in turn activates multiple genes, notably those involved in chromosome replication and segregation. The cellular concentration of DnaA is cell cycle-controlled, peaking at the time of replication initiation and gcrA induction. Regulated proteolysis of GcrA contributes to the cell cycle variations in GcrA abundance. We propose that DnaA couples DNA replication initiation with the expression of the two oscillating regulators GcrA and CtrA and that the DnaA/GcrA/ CtrA regulatory cascade drives the forward progression of the Caulobacter cell cycle.