Sequential and ordered assembly of E1 initiator complexes on the papillomavirus origin of DNA replication generates progressive structural changes related to melting
Sequential and ordered assembly of E1 initiator complexes on the papillomavirus origin of DNA replication generates progressive structural changes related to melting
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DOI：
10.1128/mcb.22.21.7712-7720.2002
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发表时间：
2002-11-01
影响因子：
5.3
通讯作者：
Stenlund, A
中科院分区：
文献类型：
--
作者：
Chen, G;Stenlund, A
起始蛋白的多个结合位点是来自各种生物体的复制子序列的共同特征。通过与复制因子结合，引发剂标记该位点，并通过很大程度上未知的机制促进DNA的熔化或扭曲。在这里，我们分析了DNA复制起点（ori）的El启动子的结合，并显示顺序结合到一组重叠的结合位点。这些引发剂复合物的组装通过逐渐降低引发剂和DNA之间的相互作用的依赖性和逐渐增加对引发剂分子之间的相互作用的依赖性来控制，提供了顺序和有序组装的机制。重要的是，引发剂的结合引起位点和位点侧翼序列的渐进性结构改变，最终产生严重的结构改变。这些结果表明，模板熔化的过程可能是递增的，其中每个引发剂分子的结合作为一个楔，结合后逐渐改变模板结构。这种机制可以解释在许多ori中观察到的多个引发剂结合位点的需要。
Multiple binding sites for an initiator protein are a common feature of replicator sequences from various organisms. By binding to the replicator, initiators mark the site and contribute to melting or distortion of the DNA by largely unknown mechanisms. Here we analyze origin of DNA replication (ori) binding by the El initiator and show sequential binding to a set of overlapping binding sites. The assembly of these initiator complexes is controlled by a gradual reduction in the dependence of interactions between the initiator and DNA and a gradual increase in the reliance on interactions between initiator molecules, providing a mechanism for sequential and orderly assembly. Importantly, the binding of the initiator causes progressive structural alterations both in the sites and in the sequences flanking the sites, eventually generating severe structural alterations. These results indicate that the process of template melting may be incremental, where binding of each initiator molecule serves as a wedge that upon binding gradually alters the template structure. This mechanism may explain the requirement for multiple initiator binding sites that is observed in many ori's.