Eukaryotic replication origins: Strength in flexibility.
Eukaryotic replication origins: Strength in flexibility.
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DOI：
10.1080/19491034.2016.1187353
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发表时间：
2016-05-03
期刊：
影响因子：
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通讯作者：
Remus D
中科院分区：
文献类型：
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作者：
Kumar C;Remus D
真核复制型DNA解旋酶Mcm 2 -7以无活性形式作为双六聚体复合物围绕双链DNA加载。为了确保复制起点在每个S期激发不超过一次，Mcm 2 -7解旋酶的激活在时间上与细胞周期中的Mcm 2 -7加载分开。这种两步机制要求非活性Mcm 2 -7复合物在染色质上以拓扑结合状态维持可变的时间段，这可能对其他DNA交易产生空间障碍。我们最近在芽殖酵母酿酒酵母中发现，Mcm 2 -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，Mcm 2 -7双六聚体在沿着DNA置换后仍保持功能，并支持从远离起点的位点开始复制。这些结果揭示了一种新的机制，指定真核生物复制起点网站，并保持复制起点的能力，而不需要Mcm 2 -7重新加载。
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.