Replication origin recognition and deformation by a heterodimeric archaeal Orc1 complex
Replication origin recognition and deformation by a heterodimeric archaeal Orc1 complex
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DOI：
10.1126/science.1143690
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发表时间：
2007-08-31
期刊：
影响因子：
56.9
通讯作者：
Berger, James M.
中科院分区：
文献类型：
--
作者：
Dueber, Erin L. Cunningham;Corn, Jacob E.;Berger, James M.
遗传物质的忠实复制依赖于必要的DNA复制起始因子。细胞启动子在复制起点上形成高阶组装体，利用三磷酸腺苷（ATP）局部重塑双链DNA，并促进合成复制体组分的适当装载。为了更好地了解引发剂的功能，我们确定了与原始DNA结合的古细菌Cdc6/Orc1异二聚体的3.4埃分辨率结构。该结构表明，除了传统的DNA结合元件外，启动子还使用它们的AAA+ atp酶结构域来识别起源DNA。这些相互作用共同建立了原点上引发剂组装的极性，并诱导了原点DNA链的实质性扭曲。生化分析和比较分析表明，在该结构中观察到的AAA+/DNA接触是动态的和进化保守的，表明该复合物是基础起始机制的核心组成部分。
The faithful duplication of genetic material depends on essential DNA replication initiation factors. Cellular initiators form higher-order assemblies on replication origins, using adenosine triphosphate ( ATP) to locally remodel duplex DNA and facilitate proper loading of synthetic replisomal components. To better understand initiator function, we determined the 3.4 angstrom-resolution structure of an archaeal Cdc6/Orc1 heterodimer bound to origin DNA. The structure demonstrates that, in addition to conventional DNA binding elements, initiators use their AAA+ ATPase domains to recognize origin DNA. Together these interactions establish the polarity of initiator assembly on the origin and induce substantial distortions into origin DNA strands. Biochemical and comparative analyses indicate that AAA+/DNA contacts observed in the structure are dynamic and evolutionarily conserved, suggesting that the complex forms a core component of the basal initiation machinery.