Initiation of DNA Replication.
Initiation of DNA Replication.
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DOI：
10.1128/ecosalplus.4.4.1
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发表时间：
2010-09
期刊：
影响因子：
--
通讯作者：
Grimwade JE
中科院分区：
文献类型：
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作者：
Leonard AC;Grimwade JE
近年来，已经清楚的是，复杂的调控电路控制DNA复制的起始步骤，通过指导组装多组分分子机器（orisome），分离DNA链和加载复制解旋酶atoriC，独特的染色体复制起点。本章讨论了最近的努力，以了解调节蛋白质-DNA相互作用，负责适当的定时启动染色体复制。它回顾了新发现的核苷酸序列特征inEscherichia coli oriC和细菌起始蛋白DnaA的新的结构和生化属性的信息。它还讨论了协调机制，防止不适当的定时DNA复制。编码启动子的基因的鉴定来自于对大肠杆菌温度敏感的条件致死突变体的研究。在大肠杆菌中鉴定出两种DNA复制缺陷型，即“立即停止”突变体和“延迟停止”突变体。延迟停止突变体的动力学表明，缺陷基因产物是DNA合成起始步骤所专门需要的，随后鉴定了两个基因：dnaA和dnaC。DnaA蛋白是细菌的启动子，而inE.在大肠杆菌中，DnaC蛋白是加载复制解旋酶所必需的。调节DnaA的可访问性tooriC，有序的组装和拆卸的多DnaA复杂的atoriC，并通过DnaA unwindsoriCremain重要的问题要回答的手段，本章讨论了目前的知识状态对这些主题。
In recent years it has become clear that complex regulatory circuits control the initiation step of DNA replication by directing the assembly of a multicomponent molecular machine (the orisome) that separates DNA strands and loads replicative helicase atoriC, the unique chromosomal origin of replication. This chapter discusses recent efforts to understand the regulated protein-DNA interactions that are responsible for properly timed initiation of chromosome replication. It reviews information about newly identified nucleotide sequence features withinEscherichia coli oriCand the new structural and biochemical attributes of the bacterial initiator protein DnaA. It also discusses the coordinated mechanisms that prevent improperly timed DNA replication. Identification of the genes that encoded the initiators came from studies on temperature-sensitive, conditional-lethal mutants ofE. coli, in which two DNA replication-defective phenotypes, "immediate stop" mutants and "delayed stop" mutants, were identified. The kinetics of the delayed stop mutants suggested that the defective gene products were required specifically for the initiation step of DNA synthesis, and subsequently, two genes,dnaAanddnaC, were identified. The DnaA protein is the bacterial initiator, and inE. coli, the DnaC protein is required to load replicative helicase. Regulation of DnaA accessibility tooriC, the ordered assembly and disassembly of a multi-DnaA complex atoriC, and the means by which DnaA unwindsoriCremain important questions to be answered and the chapter discusses the current state of knowledge on these topics.