共 34 条
Regulation of the bacterial cell cycle by an integrated genetic circuit
被引:211
作者:
Biondi, Emanuele G.
Reisinger, Sarah J.
Skerker, Jeffrey M.
Arif, Muhammad
Perchuk, Barrett S.
Ryan, Kathleen R.
Laub, Michael T.
机构:
[1] Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA
[2] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA
来源:
基金:
美国国家科学基金会;
关键词:
DNA-REPLICATION;
HISTIDINE KINASE;
POLAR LOCALIZATION;
PROTEIN;
PROGRESSION;
DIVISION;
CTRA;
D O I:
10.1038/nature05321
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
How bacteria regulate cell cycle progression at a molecular level is a fundamental but poorly understood problem. In Caulobacter crescentus, two-component signal transduction proteins are crucial for cell cycle regulation, but the connectivity of regulators involved has remained elusive and key factors are unidentified. Here we identify ChpT, an essential histidine phosphotransferase that controls the activity of CtrA, the master cell cycle regulator. We show that the essential histidine kinase CckA initiates two phosphorelays, each requiring ChpT, which lead to the phosphorylation and stabilization of CtrA. Downregulation of CckA activity therefore results in the dephosphorylation and degradation of CtrA, which in turn allow the initiation of DNA replication. Furthermore, we show that CtrA triggers its own destruction by promoting cell division and inducing synthesis of the essential regulator DivK, which feeds back to downregulate CckA immediately before S phase. Our results define a single integrated circuit whose components and connectivity can account for the cell cycle oscillations of CtrA in Caulobacter.
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页码:899 / 904
页数:6
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