Mechanisms and regulation of DNA replication initiation in eukaryotes.

Mechanisms and regulation of DNA replication initiation in eukaryotes.
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DOI:
10.1080/10409238.2016.1274717
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发表时间:
2017-04
影响因子:
6.5
通讯作者:
Berger JM
Berger JM
中科院分区:
生物学2区
文献类型:
--
作者:
Parker MW;Botchan MR;Berger JM

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细胞DNA复制是通过多蛋白复合物的作用启动的,该复合物识别染色体中的复制起始位点(称为起点)并促进这些区域内的双链体DNA解链。在一个给定的细胞周期中,每个起点仅发生一次起始,每一轮复制与细胞分裂紧密耦合。为了避免异常的起点激发和再复制,真核生物在起始过程中严格调节两个事件:通过起点识别复合物(ORC)将复制解旋酶MCM 2 -7加载到染色质上,以及随后通过掺入称为CMG的复合物来激活解旋酶。最近的工作已经开始揭示DNA上起始因子的协调和顺序交换的细节,这些交换产生了一种具有复制能力的复合物,即复制体。在这里,我们回顾了支持真核DNA复制起始的分子机制-从选择复制起始位点到复制解旋酶加载和激活-并描述了这些事件通常是如何在不同的真核模式生物中受到明显调控的。
Cellular DNA replication is initiated through the action of multiprotein complexes that recognize replication start sites in the chromosome (termed origins) and facilitate duplex DNA melting within these regions. In a given cell cycle, initiation occurs only once per origin and each round of replication is tightly coupled to cell division. To avoid aberrant origin firing and re-replication, eukaryotes tightly regulate two events in the initiation process: loading of the replicative helicase, MCM2-7, onto chromatin by the Origin Recognition Complex (ORC), and subsequent activation of the helicase by incorporation into a complex known as the CMG. Recent work has begun to reveal the details of an orchestrated and sequential exchange of initiation factors on DNA that give rise to a replication-competent complex, the replisome. Here we review the molecular mechanisms that underpin eukaryotic DNA replication initiation – from selecting replication start sites to replicative helicase loading and activation – and describe how these events are often distinctly regulated across different eukaryotic model organisms.
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