Regulation of chromosomal replication initiation by oriC-proximal DnaA-box clusters in Bacillus subtilis
Regulation of chromosomal replication initiation by oriC-proximal DnaA-box clusters in Bacillus subtilis
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DOI：
10.1093/nar/gkr716
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发表时间：
2012-01-01
影响因子：
14.9
通讯作者：
Ishikawa, Shu
中科院分区：
文献类型：
--
作者：
Okumura, Hajime;Yoshimura, Mika;Ishikawa, Shu
细菌染色体复制是通过 DnaA 与复制起点 (oriC) 内的 DnaA-box 簇 (DBC) 结合而启动的。在枯草芽孢杆菌中，在 oriC 之外发现了另外 6 个 DBC，其中一些已知参与邻近基因的转录调节。缺乏六个 DBC (Delta 6) 的缺失突变体很早就开始复制。此外，Delta 6 细胞中 spo0J 的失活产生了多效性表型，并伴有严重的生长抑制。然而，soj 中的自发抑制因子或 soj 的缺失会在 Spo0J 缺失的情况下刺激 DnaA 活性，从而抵消了这些影响。在突变体背景中没有观察到这种异常表型特征，其中复制起始是由质粒衍生的复制起点驱动的。此外，在 Delta 6 染色体内的各个异位位置引入单个 DBC 部分抑制了早期起始表型，但这取决于插入位置。我们认为，DBC 通过与 DnaA 分子相互作用来负向调节复制起始，并与 Spo0J/Soj 一起在调节 DnaA 活性中发挥重要作用。
Bacterial chromosome replication is initiated by binding of DnaA to a DnaA-box cluster (DBC) within the replication origin (oriC). In Bacillus subtilis, six additional DBCs are found outside of oriC and some are known to be involved in transcriptional regulation of neighboring genes. A deletion mutant lacking the six DBCs (Delta 6) initiated replication early. Further, inactivation of spo0J in Delta 6 cells yielded a pleiotropic phenotype, accompanied by severe growth inhibition. However, a spontaneous suppressor in soj or a deletion of soj, which stimulates DnaA activity in the absence of Spo0J, counteracted these effects. Such abnormal pheno-typic features were not observed in a mutant background in which replication initiation was driven by a plasmid-derived replication origin. Moreover, introduction of a single DBC at various ectopic positions within the Delta 6 chromosome partly suppressed the early-initiation phenotype, but this was dependent on insertion location. We propose that DBCs negatively regulate replication initiation by interacting with DnaA molecules and play a major role, together with Spo0J/Soj, in regulating the activity of DnaA.