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ParA 对 DNA 复制起始的调控与定位无关。

Regulation of DNA replication initiation by ParA is independent of location in .

机构信息

Centre for Bacterial Cell Biology, Biosciences Institute, Newcastle University, Newcastle Upon Tyne, NE2 4AX, UK.

出版信息

Microbiology (Reading). 2022 Oct;168(10). doi: 10.1099/mic.0.001259.

Abstract

Replication and segregation of the genetic information is necessary for a cell to proliferate. In , the Par system (ParA/Soj, ParB/Spo0J and ) is required for segregation of the chromosome origin () region and for proper control of DNA replication initiation. ParB binds sites clustered near the origin of replication and assembles into sliding clamps that interact with ParA to drive origin segregation through a diffusion-ratchet mechanism. As part of this dynamic process, ParB stimulates ParA ATPase activity to trigger its switch from an ATP-bound dimer to an ADP-bound monomer. In addition to its conserved role in DNA segregation, ParA is also a regulator of the master DNA replication initiation protein DnaA. We hypothesized that in the location of the Par system proximal to would be necessary for ParA to properly regulate DnaA. To test this model, we constructed a range of genetically modified strains with altered numbers and locations of sites, many of which perturbed chromosome origin segregation as expected. Contrary to our hypothesis, the results show that regulation of DNA replication initiation by ParA is maintained when a site is separated from . Because a single site is sufficient for proper control of ParA, the results are consistent with a model where ParA is efficiently regulated by ParB sliding clamps following loading at .

摘要

遗传信息的复制和分离对于细胞增殖是必要的。在 ,Par 系统(ParA/Soj、ParB/Spo0J 和 )对于染色体起始()区域的分离和适当控制 DNA 复制起始是必需的。ParB 结合聚集在复制起始附近的 位点,并组装成滑动夹,与 ParA 相互作用,通过扩散棘轮机制驱动起始分离。在这个动态过程中,ParB 刺激 ParA ATP 酶活性,触发其从结合 ATP 的二聚体转换为结合 ADP 的单体。除了在 DNA 分离中的保守作用外,ParA 也是主 DNA 复制起始蛋白 DnaA 的调节剂。我们假设在 中,Par 系统靠近 的位置对于 ParA 正确调节 DnaA 是必要的。为了验证这个模型,我们构建了一系列具有不同数量和位置的 位点的基因修饰菌株,其中许多菌株如预期的那样扰乱了染色体起始的分离。与我们的假设相反,结果表明,当一个 位点与 分离时,ParA 对 DNA 复制起始的调节仍然存在。由于单个 位点足以对 ParA 进行适当控制,因此结果与 ParB 滑动夹在加载后可以有效地调节 ParA 的模型一致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb40/7614844/84037a2e98fa/EMS179175-f001.jpg

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