DnaA, ORC, and Cdc6: similarity beyond the domains of life and diversity
DnaA, ORC, and Cdc6: similarity beyond the domains of life and diversity
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DOI：
10.1139/o09-154
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发表时间：
2010-02-01
期刊：
影响因子：
--
通讯作者：
Katayama, Tsutomu
中科院分区：
文献类型：
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作者：
Kawakami, Hironori;Katayama, Tsutomu
为了启动染色体DNA复制，特异性蛋白质结合到复制起点区域并形成多聚体和动态复合物。细菌DnaA，真核生物的起源识别复合物（ORC），和Cdc 6蛋白，其中大多数包括AAA+（-样）基序，在复制起始中起着至关重要的作用。ATP结合和水解在这些蛋白质中的重要性最近已被认识到。ATP结合的大肠杆菌DnaA是必要的，以形成一个激活形式的DnaA多聚体的复制起点。ATP-DnaA多聚体可以以来源依赖的方式解旋双链DNA，这是由几个AAA+基序的各种特定功能支持的。DnaA-ATP水解在启动后被刺激，抑制额外的启动，并维持每细胞周期一次的复制。酵母中ORC和Cdc 6的ATP结合是异源多聚体复合物形成和特异性DNA结合所必需的。这些蛋白质的ATP水解对于有效装载微型染色体维持蛋白复合物是重要的，微型染色体维持蛋白复合物是假定的复制解旋酶的组分。在这篇综述中，我们讨论了DnaA，ORC，Cdc 6在复制起始及其调节的作用。我们还总结了这些蛋白质的AAA+结构域的功能特征，以及ORC在染色体动力学中的功能分歧。
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 ofEscherichia coliDnaA 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 inSaccharomyces cerevisiaeis 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.