Bidirectional eukaryotic DNA replication is established by quasi-symmetrical helicase loading.

Bidirectional eukaryotic DNA replication is established by quasi-symmetrical helicase loading.
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DOI:
10.1126/science.aan0063
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发表时间:
2017-07-21
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Diffley JFX
Diffley JFX
中科院分区:
其他
文献类型:
--
作者:
Coster G;Diffley JFX

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真核DNA复制起始点的双向复制需要在DNA周围以相反的方向装载两个环状的微染色体维持(MCM)解旋酶。MCM加载是通过起源识别复合体(ORC)与DNA结合来协调的,但ORC如何协调对称的MCM加载尚不清楚。我们使用自然发芽酵母来源和合成序列来表明有效的MCM负载需要两个ORC分子与两个ORC结合位点的结合。这些位点的相对方向,而不是它们之间的距离,对于体外MCM负载和体内来源功能是至关重要的。我们认为,ORC准对称加载单个MCM六角体并将MCM定向易位到双六角体是建立古生代和真核生物双向复制的统一机制。
Bidirectional replication from eukaryotic DNA replication origins requires the loading of two ring-shaped Minichromosome Maintenance (MCM) helicases around DNA in opposite orientations. MCM loading is orchestrated by binding of the Origin Recognition Complex (ORC) to DNA, but how ORC coordinates symmetrical MCM loading is unclear. We used natural budding yeast origins and synthetic sequences to show that efficient MCM loading requires binding of two ORC molecules to two ORC binding sites. The relative orientation of these sites, but not the distance between them, was critical for MCM loading in vitro and origin function in vivo. We propose that quasi-symmetrical loading of individual MCM hexamers by ORC and directed MCM translocation into double hexamers acts as a unifying mechanism for the establishment of bidirectional replication in Archaea and Eukarya.
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