Structure and function of Cdc6/Cdc18: Implications for origin recognition and checkpoint control
Structure and function of Cdc6/Cdc18: Implications for origin recognition and checkpoint control
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DOI：
10.1016/s1097-2765(00)00062-9
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发表时间：
2000-09-01
期刊：
影响因子：
16
通讯作者：
Berger, JM
中科院分区：
文献类型：
--
作者：
Liu, JY;Smith, CL;Berger, JM
Cdc6/Cdc18是复制前复合物的一个保守的重要组成部分。古细菌Cdc6同源物的2.0埃晶体结构，结合对裂糖菌同源Cdc18蛋白的突变分析，揭示了Cdc6/Cdc18功能的新方面。Cdc6的两个结构域形成AAA（+）型核苷酸结合折叠，观察到与Mg ADP结合。第三个结构域采用翼状螺旋折叠，类似于已知的DNA结合模块。序列比较表明，翼状螺旋结构域在Orc1中是保守的，突变数据表明，Cdc6/Cdc18的该区域在体内的功能是必需的。额外的突变分析表明，Cdc6/Cdc18的核苷酸结合和/或水解不仅是S期进展所必需的，也是S期维持检查点控制所必需的。
Cdc6/Cdc18 is a conserved and essential component of prereplication complexes. The 2.0 Angstrom crystal structure of an archaeal Cdc6 ortholog, in conjunction with a mutational analysis of the homologous Cdc18 protein from Schizosaccharomyces pombe, reveals novel aspects of Cdc6/Cdc18 function. Two domains of Cdc6 form an AAA(+)-type nucleotide binding fold that is observed bound to Mg ADP. A third domain adopts a winged-helix fold similar to known DNA binding modules. Sequence comparisons show that the winged-helix domain is conserved in Orc1, and mutagenesis data demonstrate that this region of Cdc6/Cdc18 is required for function in vivo. Additional mutational analyses suggest that nucleotide binding and/or hydrolysis by Cdc6/Cdc18 is required not only for progression through S phase, but also for maintenance of checkpoint control during S phase.