Initiation of Escherichia coli chromosome replication is controlled by the DnaA initiator protein. Both rifampicin‐mediated inhibition of transcription and ppGpp‐induced changes in global transcription stops replication at the level of initiation. Here, we show that continued DnaA protein synthesis allows for replication initiation both during the rifampicin treatment and during the stringent response when the ppGpp level is high. A reduction in or cessation of de novo DnaA synthesis, therefore, causes the initiation arrest in both cases. In accordance with this, inhibition of translation with chloramphenicol also stops initiations. The initiation arrest caused by rifampicin was faster than that caused by chloramphenicol, despite of the latter inhibiting DnaA accumulation immediately. During chloramphenicol treatment transcription is still ongoing and we suggest that transcriptional events in or near the origin, that is, transcriptional activation, can allow for a few extra initiations when DnaA becomes limiting. We suggest, for both rifampicin treated cells and for cells accumulating ppGpp, that a turn‐off of initiation from oriC requires a stop in de novo DnaA synthesis and that an additional lack of transcriptional activation enhances this process, that is, leads to a faster initiation stop.

中文翻译：

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通过从头合成 DnaA 蛋白质，可以克服利福平处理或严格反应期间对大肠杆菌染色体复制的抑制。

大肠杆菌的引发染色体复制由 DnaA 起始蛋白控制。利福平介导的转录抑制和 ppGpp 诱导的全局转录变化都会在起始水平停止复制。在这里，我们展示了持续的 DnaA 蛋白质合成允许在利福平治疗期间和在 ppGpp 水平高时的严格反应期间复制起始。因此，在这两种情况下，从头 DnaA 合成的减少或停止都会导致起始停止。据此，用氯霉素抑制翻译也会停止起始。利福平引起的起始阻滞比氯霉素引起的起始阻滞更快，尽管后者立即抑制了 DnaA 的积累。在氯霉素处理期间，转录仍在进行中，我们建议在起源处或附近的转录事件，即转录激活，可以在 DnaA 变得受限时允许一些额外的起始。我们建议，对于利福平处理的细胞和积累 ppGpp 的细胞，关闭从oriC需要在从头 DnaA 合成中停止，并且额外缺乏转录激活会增强该过程，即导致更快的起始停止。