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Cyclic di-GMP acts as a cell cycle oscillator to drive chromosome replication

机译：循环双GMP充当细胞周期振荡器，以驱动染色体复制

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摘要

Fundamental to all living organisms is the capacity to coordinate cell division and cell differentiation to generate appropriate numbers of specialized cells. Whereas eukaryotes use cyclins and cyclin-dependent kinases to balance division with cell fate decisions(1), equivalent regulatory systems have not been described in bacteria. Moreover, the mechanisms used by bacteria to tune division in line with developmental programs are poorly understood. Here we show that Caulobacter crescentus, a bacterium with an asymmetric division cycle, uses oscillating levels of the second messenger cyclic diguanylate (c-di-GMP) to drive its cell cycle. We demonstrate that c-diGMP directly binds to the essential cell cycle kinase CckA to inhibit kinase activity and stimulate phosphatase activity. An upshift of c-di-GMP during the G1-S transition switches CckA from the kinase to the phosphatase mode, thereby allowing replication initiation and cell cycle progression. Finally, we show that during division, c-di-GMP imposes spatial control on CckA to install the replication asymmetry of future daughter cells. These studies reveal c-di-GMP to be a cyclin-like molecule in bacteria that coordinates chromosome replication with cell morphogenesis in Caulobacter. The observation that c-di-GMP-mediated control is conserved in the plant pathogen Agrobacterium tumefaciens suggests a general mechanism through which this global regulator of bacterial virulence and persistence coordinates behaviour and cell proliferation.
机译：对所有活生物体而言，根本的能力是协调细胞分裂和细胞分化以生成适当数量的专门细胞的能力。尽管真核生物使用细胞周期蛋白和细胞周期蛋白依赖性激酶来平衡细胞命运决定与分裂（1），但在细菌中尚未描述等效的调控系统。此外，人们对细菌根据发育程序调节分裂所用的机理了解甚少。在这里，我们显示月牙芽孢杆菌（Caulobacter crescentus）是一种具有不对称分裂周期的细菌，它使用第二信使环状双鸟苷酸（c-di-GMP）的振荡水平来驱动其细胞周期。我们证明c-diGMP直接结合到必需的细胞周期激酶CckA，以抑制激酶活性并刺激磷酸酶活性。在G1-S转换过程中c-di-GMP的上移将CckA从激酶切换为磷酸酶模式，从而实现复制起始和细胞周期进程。最后，我们表明，在分裂过程中，c-di-GMP对CckA施加了空间控制，以安装未来子细胞的复制不对称性。这些研究表明，c-di-GMP是细菌中的一种细胞周期蛋白样分子，可协调杆状细菌中染色体复制与细胞形态发生。 c-di-GMP介导的控制在植物病原土壤杆菌土壤杆菌中得以保留的观察结果表明，这种细菌毒力和持久性全局调节剂通过其协调行为和细胞增殖的一般机制。

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  • 来源
    《Nature》 |2015年第7559期|236-239|共4页
  • 作者

    Lori C.; Ozaki S.; Steiner S.; Boehm R.; Abel S.; Dubey B. N.; Schirmer T.; Hiller S.; Jenal U.;

  • 作者单位

    Univ Basel, Biozentrum, Focal Area Infect Biol, CH-4056 Basel, Switzerland;

    Univ Basel, Biozentrum, Focal Area Infect Biol, CH-4056 Basel, Switzerland;

    Univ Basel, Biozentrum, Focal Area Infect Biol, CH-4056 Basel, Switzerland;

    Univ Basel, Biozentrum, Focal Area Struct Biol & Biophys, CH-4056 Basel, Switzerland;

    Univ Basel, Biozentrum, Focal Area Infect Biol, CH-4056 Basel, Switzerland;

    Univ Basel, Biozentrum, Focal Area Struct Biol & Biophys, CH-4056 Basel, Switzerland;

    Univ Basel, Biozentrum, Focal Area Struct Biol & Biophys, CH-4056 Basel, Switzerland;

    Univ Basel, Biozentrum, Focal Area Struct Biol & Biophys, CH-4056 Basel, Switzerland;

    Univ Basel, Biozentrum, Focal Area Infect Biol, CH-4056 Basel, Switzerland;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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