Cell size and the initiation of DNA replication in bacteria.
Cell size and the initiation of DNA replication in bacteria.
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细胞大小和细菌中DNA复制的启动。
DOI：
10.1371/journal.pgen.1002549
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Levin PA
中科院分区：
文献类型：
--
作者：
Hill NS;Kadoya R;Chattoraj DK;Levin PA
在真核生物中，DNA复制通过细胞周期蛋白依赖性激酶和相关因子的作用与细胞周期偶联。在细菌中，主要基于大肠杆菌的工作的流行观点是高度保守的启动子DnaA的生长依赖性积累触发了启动。然而，在比野生型细胞小约30%的枯草芽孢杆菌突变体中，起始的时间是不变的，这表明实现特定的细胞大小对于起始不是必须的。基于这一发现，我们重新研究了E. coli和B.枯草杆菌。虽然DNA复制的改变已经被证明可以改变E. coli和B.枯草杆菌细胞大小，相反的情况（细胞大小对DNA复制的影响）尚未探讨。在这里，我们报告说，负责协调DNA复制与细胞大小的机制在这两种模式生物之间各不相同。与B相反。subtilis、小E.大肠杆菌突变体延迟复制起始，直到它们达到野生型细胞起始的大小。DnaA的适度增加缓解了延迟，支持DnaA的生长依赖性积累是E.杆菌虽然小E。coli和B. subtilis细胞均保持野生型DnaA浓度，只有E.大肠杆菌突变株未能及时启动。因此，DnaA的总量似乎比浓度对E.杆菌这两种细菌的行为差异似乎在于控制DnaA活性的机制。DNA复制必须与生长和分裂相协调，以确保细胞和生物体的活力。在细菌中，据信DNA复制起始物DnaA的细胞生长依赖性积累到临界水平决定了起始时间。这一观点主要基于来自模式细菌E.大肠杆菌，它只有在达到特定大小时才启动复制。然而，最近的数据从另一个模式生物，B。枯草芽孢杆菌的DNA复制，其中DnaA也是起始的速率限制，表明细胞大小的变化可能不会影响DNA复制的时间。这一发现促使我们重新审视E.杆菌虽然以前的研究考察了DNA复制对细胞大小的扰动，但我们确定了细胞大小缺陷对DNA复制的影响。这种匡威的方法得出的结论是，无论大小，DnaA需要积累到一个临界量，以触发启动E。大肠杆菌，正如人们普遍认为的那样。相比之下，小B.枯草杆菌细胞能以比野生型少30%的DnaA启动复制。因此，虽然DnaA在两种生物体中都是起始速率限制性的，但控制其活性的机制在不同的细菌中可能不同。
In eukaryotes, DNA replication is coupled to the cell cycle through the actions of cyclin-dependent kinases and associated factors. In bacteria, the prevailing view, based primarily from work in Escherichia coli, is that growth-dependent accumulation of the highly conserved initiator, DnaA, triggers initiation. However, the timing of initiation is unchanged in Bacillus subtilis mutants that are ∼30% smaller than wild-type cells, indicating that achievement of a particular cell size is not obligatory for initiation. Prompted by this finding, we re-examined the link between cell size and initiation in both E. coli and B. subtilis. Although changes in DNA replication have been shown to alter both E. coli and B. subtilis cell size, the converse (the effect of cell size on DNA replication) has not been explored. Here, we report that the mechanisms responsible for coordinating DNA replication with cell size vary between these two model organisms. In contrast to B. subtilis, small E. coli mutants delayed replication initiation until they achieved the size at which wild-type cells initiate. Modest increases in DnaA alleviated the delay, supporting the view that growth-dependent accumulation of DnaA is the trigger for replication initiation in E. coli. Significantly, although small E. coli and B. subtilis cells both maintained wild-type concentration of DnaA, only the E. coli mutants failed to initiate on time. Thus, rather than the concentration, the total amount of DnaA appears to be more important for initiation timing in E. coli. The difference in behavior of the two bacteria appears to lie in the mechanisms that control the activity of DnaA. DNA replication must be coordinated with growth and division to ensure the viability of cells and organisms. In bacteria, it is believed that cell growth–dependent accumulation of the initiator of DNA replication, DnaA, to critical levels determines the timing of initiation. This view is based primarily on data from the model bacterium E. coli, which initiates replication only upon achieving a particular size. However, recent data from another model organism, B. subtilis, where DnaA is also rate limiting for initiation, suggests that changes in cell size may not impact the timing of DNA replication. This finding prompted us to revisit the relationship between cell size and DNA replication in E. coli. While previous studies examined perturbations in DNA replication on cell size, we instead determined the consequences of cell size defects on DNA replication. This converse approach led to the conclusion that, irrespective of size, DnaA needs to accumulate to a critical amount to trigger initiation in E. coli, as is generally believed to be the case. In contrast, small B. subtilis cells could initiate replication with amounts of DnaA ∼30% less than wild type. Thus, while DnaA is rate limiting for initiation in both organisms, the mechanisms controlling its activity may vary in different bacteria.
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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：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
Ishikawa, Shu
影响因子：
4.1
作者：
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通讯作者：
Ogasawara, Naotake
影响因子：
7.7
作者：
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通讯作者：
Crooke, E