1887

Abstract

The master regulator CtrA oscillates during the cell 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 native locus that prevents transcription from P1 but not P2. As expected, the P1 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 the P1 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 of transcription despite low levels of CtrA and increased transcription of P2 in the P1 mutant are two examples of robustness in the cell cycle. Thus, can adjust regulatory pathways to partially compensate for reduced and delayed CtrA accumulation in the P1 mutant.

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2012-10-01
2020-01-26
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