Recruitment and activation of DnaB helicase in Escherichia coli DNA replication

描述（由申请人提供）：所有细胞生物体都依赖于称为复制体的多蛋白质分子机器来复制其基因组。在复制起点，染色体DNA复制的复制体组装是与细胞周期协调的高度调节事件。在大肠杆菌中，DnaA蛋白通过协调导致两个DNA解旋酶结合到每个亲本DNA链的逐步过程来启动染色体DNA复制，这对于从染色体起点的双向分叉运动是必需的。复制体的其他组成部分然后在新形成的复制叉处组装。基因组的复制随之而来。 在DNA复制的起始阶段，复制解旋酶向染色体起点的募集是关键步骤。本研究的长期目标是通过遗传学、生物化学和分子生物学方法，了解大肠杆菌复制性解旋酶DnaB的募集和激活的分子机制。因为所有自由生活的生物体都使用类似的启动机制，这些研究应该提供关于这一事件如何在高等生物体中发生的见解。

DESCRIPTION (provided by applicant): All cellular organisms rely on a multi-protein molecular machine named the replisome to duplicate their genomes. At replication origins, assembly of replisomes for chromosomal DNA replication is a highly regulated event that is coordinated with the cell cycle. In Escherichia coli, DnaA protein initiates chromosomal DNA replication by orchestrating a step-wise process that leads to two DNA helicases bound to each parental DNA strand, which is necessary for bidirectional fork movement from the chromosomal origin. Other components of the replisome then assemble at the newly formed replication fork. Duplication of the genome follows. The recruitment of the replicative helicase to the chromosomal origin is a critical step during the initiation stage of DNA replication. The long-term objective of this research is to understand the molecular mechanism of recruitment and activation of DnaB, the replicative helicase of Escherichia coli, via genetic, biochemical and molecular biological methods. Because all free-living organisms use a similar mechanism of initiation, these studies should provide insight into how this event occurs in higher organisms.