Modularity of the bacterial cell cycle enables independent spatial and temporal control of DNA replication.

Modularity of the bacterial cell cycle enables independent spatial and temporal control of DNA replication.
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DOI:
10.1016/j.cub.2011.05.040
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发表时间:
2011-07-12
期刊:
影响因子:
9.2
通讯作者:
Laub, Michael T.
Laub, Michael T.
中科院分区:
生物学1区
文献类型:
--
作者:
Jonas, Kristina;Chen, Y. Erin;Laub, Michael T.

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生物学中复杂的调节回路通常由更简单的子回路或模块组成。在大多数情况下,模块化的功能后果和进化起源仍然没有得到很好的定义。在这里,通过将单细胞显微镜与遗传方法相结合,我们证明了两个可分离的模块独立地支配不对称分裂细菌新月柄杆菌中DNA复制的时空控制。DNA复制控制涉及促进起始的DnaA和沉默起始的CtrA。我们发现,DnaA活性的振荡决定了复制的周期性,而CtrA则决定了子细胞的不对称复制命运。重要的是,我们证明了DnaA活性振荡独立于CtrA。柄杆菌属空间和时间控制模块的遗传分离性反映了它们的进化历史。DnaA是一个古老的和遗传学上广泛分布的电路的核心组成部分,它控制着柄杆菌和大多数其他细菌的复制周期。相比之下,CtrA只存在于不对称分裂的α-变形菌中,它在进化后期被整合到子细胞中,以加强复制的不对称性。
Complex regulatory circuits in biology are often built of simpler sub-circuits, or modules. In most cases, the functional consequences and evolutionary origins of modularity remain poorly defined. Here, by combining single-cell microscopy with genetic approaches, we demonstrate that two separable modules independently govern the temporal and spatial control of DNA replication in the asymmetrically dividing bacterium Caulobacter crescentus. DNA replication control involves DnaA, which promotes initiation, and CtrA, which silences initiation. We show that oscillations in DnaA activity dictate the periodicity of replication while CtrA governs the asymmetric replicative fates of daughter cells. Importantly, we demonstrate that DnaA activity oscillates independently of CtrA. The genetic separability of spatial and temporal control modules in Caulobacter reflects their evolutionary history. DnaA is the central component of an ancient and phylogenetically widespread circuit that governs replication periodicity in Caulobacter and most other bacteria. By contrast, CtrA, which is found only in the asymmetrically dividing α-proteobacteria, was integrated later in evolution to enforce replicative asymmetry on daughter cells.
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