Cold Spring Harbor Laboratory, 1 Bungtown Rd., Cold Spring Harbor, NY 11724, USA.
Biochem Cell Biol. 2010 Feb;88(1):49-62. doi: 10.1139/o09-154.
To initiate chromosomal DNA replication, specific proteins bind to the replication origin region and form multimeric and dynamic complexes. Bacterial DnaA, the eukaryotic origin recognition complex (ORC), and Cdc6 proteins, most of which include an AAA+(-like) motif, play crucial roles in replication initiation. The importance of ATP binding and hydrolysis in these proteins has recently become recognized. ATP binding of Escherichia coli DnaA is required for the formation of the activated form of a DnaA multimer on the replication origin. The ATP-DnaA multimer can unwind duplex DNA in an origin-dependent manner, which is supported by various specific functions of several AAA+ motifs. DnaA-ATP hydrolysis is stimulated after initiation, repressing extra initiations, and sustaining once-per-cell cycle replication. ATP binding of ORC and Cdc6 in Saccharomyces cerevisiae is required for heteromultimeric complex formation and specific DNA binding. ATP hydrolysis of these proteins is important for the efficient loading of the minichromosome maintenance protein complex, a component of the putative replicative helicase. In this review, we discuss the roles of DnaA, ORC, and Cdc6 in replication initiation and its regulation. We also summarize the functional features of the AAA+ domains of these proteins, and the functional divergence of ORC in chromosomal dynamics.
为了启动染色体 DNA 复制，特定的蛋白质结合到复制原点区域，并形成多聚体和动态复合物。细菌 DnaA、真核起始识别复合物 (ORC) 和 Cdc6 蛋白在复制起始中起着至关重要的作用，其中大多数蛋白包含一个 AAA+（类似）结构域。这些蛋白中 ATP 结合和水解的重要性最近才被认识到。Escherichia coli DnaA 的 ATP 结合对于在复制原点上形成 DnaA 多聚体的激活形式是必需的。ATP-DnaA 多聚体可以以依赖于原点的方式解开双链 DNA，这得到了几个 AAA+结构域的各种特定功能的支持。起始后，DnaA-ATP 水解被刺激，抑制额外的起始，并维持每个细胞周期一次的复制。酿酒酵母 ORC 和 Cdc6 的 ATP 结合对于异源多聚体复合物的形成和特定的 DNA 结合是必需的。这些蛋白的 ATP 水解对于微染色体维持蛋白复合物的有效加载很重要，微染色体维持蛋白复合物是假定复制解旋酶的一个组成部分。在这篇综述中，我们讨论了 DnaA、ORC 和 Cdc6 在复制起始及其调控中的作用。我们还总结了这些蛋白的 AAA+结构域的功能特征，以及 ORC 在染色体动力学中的功能分化。
