The eukaryotic Mcm2-7 replicative helicase.
The eukaryotic Mcm2-7 replicative helicase.
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DOI：
10.1007/978-94-007-4572-8_7
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发表时间：
2012-01-01
影响因子：
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通讯作者：
Schwacha, Anthony
中科院分区：
文献类型：
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作者：
Vijayraghavan, Sriram;Schwacha, Anthony
在真核生物中，Mcm 2 -7复合物形成了复制解旋酶的核心-分子马达，其使用ATP结合和水解来为复制叉处的双链DNA的解旋提供燃料。虽然它是一个环形的六聚体解旋酶表面上类似于更好地研究同源六聚体解旋酶从原核生物和病毒，Mcm 2 -7是唯一已知的解旋酶形成的六个独特的和必要的亚基。最近对Mcm 2 -7和含有额外激活蛋白的高阶复合物（CMG复合物）的生化和结构分析揭示了这种独特亚基组装背后的原因：DNA解旋仅需要有限数量的特定ATP酶活性位点，而一个特定的ATP酶活性位点已经进化形成环形复合物中的可逆不连续性（门）。Mcm 2 -7解旋酶在S期的激活需要辅助蛋白Cdc 45和GINS的物理关联;结构数据表明，这些辅助因子通过关闭Mcm 2 -7门激活DNA解旋。此外，利用真核生物DNA复制的生化重建进展的研究表明，Mcm 2 -7在起始期间作为双六聚体加载到起点上，但在延伸期间不作为双链DNA泵。
In eukaryotes, the Mcm2-7 complex forms the core of the replicative helicase - the molecular motor that uses ATP binding and hydrolysis to fuel the unwinding of double-stranded DNA at the replication fork. Although it is a toroidal hexameric helicase superficially resembling better-studied homohexameric helicases from prokaryotes and viruses, Mcm2-7 is the only known helicase formed from six unique and essential subunits. Recent biochemical and structural analyses of both Mcm2-7 and a higher-order complex containing additional activator proteins (the CMG complex) shed light on the reason behind this unique subunit assembly: whereas only a limited number of specific ATPase active sites are needed for DNA unwinding, one particular ATPase active site has evolved to form a reversible discontinuity (gate) in the toroidal complex. The activation of Mcm2-7 helicase during S-phase requires physical association of the accessory proteins Cdc45 and GINS; structural data suggest that these accessory factors activate DNA unwinding through closure of the Mcm2-7 gate. Moreover, studies capitalizing on advances in the biochemical reconstitution of eukaryotic DNA replication demonstrate that Mcm2-7 loads onto origins during initiation as a double hexamer, yet does not act as a double-stranded DNA pump during elongation.