We have characterised the interaction of the Aeropyrum pernix origin recognition complex proteins (ORC1 and ORC2) with DNA using DNase I footprinting. Each protein binds upstream of its respective gene. However, ORC1 protein alone interacts more tightly with an additional region containing multiple origin recognition box (ORB) sites that we show to be a replication origin. At this origin, there are four ORB elements disposed either side of an A+T-rich region. An ORC1 protein dimer binds at each of these ORB sites. Once all four ORB sites have bound ORC1 protein, there is a transition to a higher-order assembly with a defined alteration in topology and superhelicity. Furthermore, after this transition, the A+T-rich region becomes sensitive to digestion by DNase I and P1 nuclease, revealing that the transition promotes distortion of the DNA in this region, presumably as a prelude to loading of MCM helicase.

译文

我们使用DNase I足迹表征了Aeropyrum pernix起源识别复合物蛋白 (ORC1和ORC2) 与DNA的相互作用。每种蛋白质结合其各自基因的上游。然而,仅ORC1蛋白与包含多个起源识别框 (ORB) 位点的其他区域的相互作用更紧密,我们证明这是复制起源。在这个起源处,富含A T的区域的两侧都有四个ORB元素。ORC1蛋白二聚体在每个ORB位点结合。一旦所有四个ORB位点都结合了ORC1蛋白,就会过渡到具有定义的拓扑和超螺旋性变化的高阶组装。此外,在这种转变之后,富含A T的区域对DNase I和P1核酸酶的消化变得敏感,这表明该转变促进了该区域中DNA的扭曲,大概是MCM解旋酶加载的前奏。

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