The Caulobacter crescentus ctrA P1 promoter is essential for the coordination of cell cycle events that prevent the overinitiation of DNA replication.

The Caulobacter crescentus ctrA P1 promoter is essential for the coordination of cell cycle events that prevent the overinitiation of DNA replication.
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新月柄杆菌 ctrA P1 启动子对于协调细胞周期事件至关重要,防止 DNA 复制过度启动。

DOI:
10.1099/mic.0.055285-0
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发表时间:
2012
期刊:
Microbiology (Reading, England)
影响因子:
--
通讯作者:
Murray,SeanR
Murray,SeanR
中科院分区:
--
文献类型:
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作者:
Schredl,AlexanderT;PerezMora,YannetG;Herrera,Anabel;Cuajungco,MathP;Murray,SeanR

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由于临时调节的蛋白水解和转录,主调节器 CtrA 在柄杆菌细胞周期中发生振荡。它在 G1-S 转变期间被蛋白水解,并由于两个顺序激活的启动子 P1 和 P2 的转录而在分裂前细胞中重新积累。 CtrA 通过直接介导 P2 的激活并同时抑制 P1 来增强其自身的合成。为了探索 P1 在细胞周期控制中的作用,我们在 nativectrAlocus 中设计了一个突变,该突变可以阻止 P1 的转录,但不能阻止 P2 的转录。正如预期的那样,thectrAP1 突变体表现出惊人的生长、形态和 DNA 复制缺陷。出乎意料的是,我们发现ctrAP1突变体中CtrA及其拮抗剂SciP的积累显着减少,但DnaA、GcrA或CcrM的积累却没有显着减少。 SciP 水平与 CtrA 积累密切相关,表明 CtrA 作为变阻器来调节 SciP 丰度。此外,在同步培养中,P1突变体中CtrA和CcrM在预分裂细胞中的再现延迟了0.125个细胞周期单位。尽管 CtrA 水平较低,但 ccrM 转录水平较高,ctrAP1 突变体中 ctrAP2 转录增加,这是细胞周期稳健性的两个例子。因此,茎杆菌可以调整调控途径,以部分补偿 ctrAP1 突变体中 CtrA 积累的减少和延迟。
The master regulator CtrA oscillates during theCaulobactercell cycle due to temporally regulated proteolysis and transcription. It is proteolysed during the G1–S transition and reaccumulates in predivisional cells as a result of transcription from two sequentially activated promoters, P1 and P2. CtrA reinforces its own synthesis by directly mediating the activation of P2 concurrently with repression of P1. To explore the role of P1 in cell cycle control, we engineered a mutation into the nativectrAlocus that prevents transcription from P1 but not P2. As expected, thectrAP1 mutant exhibits striking growth, morphological and DNA replication defects. Unexpectedly, we found CtrA and its antagonist SciP, but not DnaA, GcrA or CcrM accumulation to be dramatically reduced in thectrAP1 mutant. SciP levels closely paralleled CtrA accumulation, suggesting that CtrA acts as a rheostat to modulate SciP abundance. Furthermore, the reappearance of CtrA and CcrM in predivisional cells was delayed in the P1 mutant by 0.125 cell cycle unit in synchronized cultures. High levels ofccrMtranscription despite low levels of CtrA and increased transcription ofctrAP2 in thectrAP1 mutant are two examples of robustness in the cell cycle. Thus,Caulobactercan adjust regulatory pathways to partially compensate for reduced and delayed CtrA accumulation in thectrAP1 mutant.