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Eukaryotic replication origins: Strength in flexibility

机译:真核复制的起源:灵活性的增强

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摘要

The eukaryotic replicative DNA helicase, Mcm2-7, is loaded in inactive form as a double hexameric complex around double-stranded DNA. To ensure that replication origins fire no more than once per S phase, activation of the Mcm2-7 helicase is temporally separated from Mcm2-7 loading in the cell cycle. This 2-step mechanism requires that inactive Mcm2-7 complexes be maintained for variable periods of time in a topologically bound state on chromatin, which may create a steric obstacle to other DNA transactions. We have recently found in the budding yeast, Saccharomyces cerevisiae, that Mcm2-7 double hexamers can respond to collisions with transcription complexes by sliding along the DNA template. Importantly, Mcm2-7 double hexamers remain functional after displacement along DNA and support replication initiation from sites distal to the origin. These results reveal a novel mechanism to specify eukaryotic replication origin sites and to maintain replication origin competence without the need for Mcm2-7 reloading.
机译:真核复制DNA解旋酶Mcm2-7以无活性的形式作为围绕双链DNA的双六聚体复合物装载。为确保复制起点在每个S期激发不超过一次,在细胞周期中,Mcm2-7解旋酶的激活与Mcm2-7的装载暂时分开。这种两步机制要求在染色质上以拓扑绑定状态将无活性的Mcm2-7复合物维持可变的时间段,这可能对其他DNA交易产生空间障碍。我们最近在萌芽的酿酒酵母中发现,Mcm2-7双六聚体可以通过沿着DNA模板滑动来响应与转录复合物的碰撞。重要的是,Mcm2-7双六聚体在沿着DNA移位后仍保持功能,并支持从起点远端的位点开始复制。这些结果揭示了一种新颖的机制,可以指定真核复制起点,并保持复制起点的能力,而无需重新加载Mcm2-7。

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