Multiple regulatory systems coordinate DNA replication with cell growth in Bacillus subtilis.
Multiple regulatory systems coordinate DNA replication with cell growth in Bacillus subtilis.
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多个调节系统将DNA复制与枯草芽孢杆菌中的细胞生长进行协调。
DOI：
10.1371/journal.pgen.1004731
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发表时间：
2014-10
期刊：
影响因子：
4.5
通讯作者：
Koh A
中科院分区：
文献类型：
--
作者：
Murray H;Koh A
在许多细菌中，DNA复制的速度与细胞生理有关，以确保基因组复制与生长相协调。几十年来，人们一直认识到营养物质介导的DNA复制启动的生长速度控制，但连接这些细胞周期活动的机制(S)一直难以理解。为了帮助解决这个根本问题，我们研究了模式生物枯草芽孢杆菌中DNA复制的调节。与流行的观点相反，我们发现Dna A蛋白水平的变化不足以解释营养介导的DNA复制起始的生长速度控制，尽管这一调控确实需要Dna A和内源复制起点。我们继续报告DNA复制与细菌快速生长所需的几种基本细胞活动之间的联系，包括呼吸、中心碳代谢、脂肪酸合成、磷脂合成和蛋白质合成。出人意料的是，结果表明，多个调节系统参与协调DNA复制和细胞生理，其中一些调节系统针对ORIC，而另一些调节系统以ORIC独立的方式发挥作用。我们建议利用不同的调控系统来控制DNA复制，以响应不同的生理和化学变化。DNA复制必须与细胞生理相协调，以确保适当的基因组遗传。模式细菌，如生活在土壤中的枯草芽孢杆菌，可以实现广泛的生长速度，以响应营养和化学信号。为了使DNA合成速率与营养物质介导的细胞生长速率相匹配，细菌调节DNA复制的起始频率。这种对细菌DNA复制启动的控制是在40多年前首次观察到的，然而这种调控的分子基础仍然存在激烈的争论。在本文中，我们测试了细菌中营养物质介导的生长速度调节的主要模型之一，即主要DNA复制起始蛋白DNAA的丰度决定了DNA复制事件的频率。关键的是，我们的结果表明，DNAA蛋白水平的变化不足以解释营养物质对枯草杆菌DNA复制启动的生长速度调节。然后，我们进一步证明了DNA复制与几种基本的细胞活动之间有很强的联系，这出人意料地表明，可能有不止一条调控途径参与协调DNA复制与细胞生理。我们相信，我们的工作改变了人们对这个长期存在的生物学问题的看法，并重新启动了对这些关键调控系统的分子基础的探索。
In many bacteria the rate of DNA replication is linked with cellular physiology to ensure that genome duplication is coordinated with growth. Nutrient-mediated growth rate control of DNA replication initiation has been appreciated for decades, however the mechanism(s) that connects these cell cycle activities has eluded understanding. In order to help address this fundamental question we have investigated regulation of DNA replication in the model organism Bacillus subtilis. Contrary to the prevailing view we find that changes in DnaA protein level are not sufficient to account for nutrient-mediated growth rate control of DNA replication initiation, although this regulation does require both DnaA and the endogenous replication origin. We go on to report connections between DNA replication and several essential cellular activities required for rapid bacterial growth, including respiration, central carbon metabolism, fatty acid synthesis, phospholipid synthesis, and protein synthesis. Unexpectedly, the results indicate that multiple regulatory systems are involved in coordinating DNA replication with cell physiology, with some of the regulatory systems targeting oriC while others act in a oriC-independent manner. We propose that distinct regulatory systems are utilized to control DNA replication in response to diverse physiological and chemical changes. DNA replication must be coordinated with cellular physiology to ensure proper genome inheritance. Model bacteria such as the soil-dwelling Bacillus subtilis can achieve a wide range of growth rates in response to nutritional and chemical signals. In order to match the rate of DNA synthesis to the rate of nutrient-mediated cell growth, bacteria regulate the initiation frequency of DNA replication. This control of bacterial DNA replication initiation was first observed over forty years ago, however the molecular basis for this regulation has remained hotly debated. In this paper we test one of the leading models for nutrient-mediated growth rate regulation in bacteria, namely that the abundance of the master DNA replication initiation protein DnaA dictates the frequency of DNA replication events. Critically, our results show that changes in DnaA protein level are not sufficient to account for nutrient-mediated growth rate regulation of DNA replication initiation in B. subtilis. We then go on to show that there are strong connections between DNA replication and several essential cellular activities, which unexpectedly indicates that there is likely more than one single regulatory pathway involved in coordinating DNA replication with cell physiology. We believe that our work changes thinking regarding this long-standing biological question and reinvigorates the search for the molecular basis of these critical regulatory systems.
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影响因子：
10.5
作者：
Leonard AC;Grimwade JE
通讯作者：
Grimwade JE
通过细菌启动器拉伸的DNA促进了复制起源。
影响因子：
64.8
作者：
Duderstadt, Karl E.;Chuang, Kevin;Berger, James M.
通讯作者：
Berger, James M.
细胞大小和细菌中DNA复制的启动。
影响因子：
4.5
作者：
Hill NS;Kadoya R;Chattoraj DK;Levin PA
通讯作者：
Levin PA
影响因子：
7
作者：
Muntel, Jan;Fromion, Vincent;Becher, Doerte
通讯作者：
Becher, Doerte
DOI：
10.1073/pnas.122040799
发表时间：
2002-06-11
影响因子：
11.1
作者：
Noirot-Gros, MF;Dervyn, E;Noirot, P
通讯作者：
Noirot, P