Burkholder W F, Kurtser I, Grossman A D
Department of Biology, Massachusetts Institute of Technology, Building 68, Room 530, Cambridge, MA 02139, USA.
Cell. 2001 Jan 26;104(2):269-79. doi: 10.1016/s0092-8674(01)00211-2.
We identified a signaling pathway that prevents initiation of sporulation in Bacillus subtilis when replication initiation is impaired. We isolated mutations that allow a replication initiation mutant (dnaA) to sporulate. These mutations affect a small open reading frame, sda, that was overexpressed in replication initiation mutants and appears to be directly regulated by DnaA. Mutations in replication initiation genes inhibit the onset of sporulation by preventing activation of a transcription factor required for sporulation, Spo0A. Deletion of sda restored activation of Spo0A in replication initiation mutants. Overexpression of sda in otherwise wild-type cells inhibited activation of Spo0A and sporulation. Purified Sda inhibited a histidine kinase needed for activation of Spo0A. Our results indicate that control of sda by DnaA establishes a checkpoint that inhibits activation of Spo0A and prevents futile attempts to initiate sporulation.
我们鉴定出了一条信号通路，当复制起始受损时，该通路可阻止枯草芽孢杆菌中芽孢形成的起始。我们分离出了一些突变，这些突变能使复制起始突变体（dnaA）形成芽孢。这些突变影响一个小的开放阅读框sda，它在复制起始突变体中过表达，并且似乎直接受DnaA调控。复制起始基因中的突变通过阻止芽孢形成所需的转录因子Spo0A的激活来抑制芽孢形成的起始。缺失sda可恢复复制起始突变体中Spo0A的激活。在其他方面为野生型的细胞中过表达sda会抑制Spo0A的激活和芽孢形成。纯化的Sda抑制激活Spo0A所需的组氨酸激酶。我们的结果表明，DnaA对sda的调控建立了一个检查点，该检查点抑制Spo0A的激活，并防止徒劳地尝试起始芽孢形成。
