Hda inactivation of DnaA is the predominant mechanism preventing hyperinitiation of Escherichia coli DNA replication
Hda inactivation of DnaA is the predominant mechanism preventing hyperinitiation of Escherichia coli DNA replication
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DOI：
10.1038/sj.embor.7400467
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发表时间：
2005-08-01
期刊：
影响因子：
7.7
通讯作者：
Crooke, E
中科院分区：
文献类型：
--
作者：
Camara, JE;Breier, AM;Crooke, E
从大肠杆菌染色体起点开始的DNA复制受到高度调节，确保每个细胞周期精确地发生一次复制。已经提出了三种调节复制起始的机制：由datA位点滴定游离DnaA起始蛋白，由SeqA蛋白隔离新复制的起点和DnaA的调节失活（RIDA），其中活性ATP-DnaA转化为无活性ADP结合形式。DNA微阵列分析表明，缺乏datA的快速生长细胞的起始水平与野生型细胞的起始水平没有区别，而缺乏SeqA蛋白只引起起始水平的适度增加，与流式细胞术数据一致。相比之下，缺乏Hda的细胞过度启动复制的两倍，牵连RIDA作为主要机制，防止额外的起始事件在细胞周期。
Initiation of DNA replication from the Escherichia coli chromosomal origin is highly regulated, assuring that replication occurs precisely once per cell cycle. Three mechanisms for regulation of replication initiation have been proposed: titration of free DnaA initiator protein by the datA locus, sequestration of newly replicated origins by SeqA protein and regulatory inactivation of DnaA (RIDA), in which active ATP-DnaA is converted to the inactive ADP-bound form. DNA microarray analyses showed that the level of initiation in rapidly growing cells that lack datA was indistinguishable from that in wild-type cells, and that the absence of SeqA protein caused only a modest increase in initiation, in agreement with flow-cytometry data. In contrast, cells lacking Hda overinitiated replication twofold, implicating RIDA as the predominant mechanism preventing extra initiation events in a cell cycle.