Two Distinct Modes of DNA Binding by an MCM Helicase Enable DNA Translocation.

Two Distinct Modes of DNA Binding by an MCM Helicase Enable DNA Translocation.
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DOI:
10.3390/ijms232314678
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发表时间:
2022-11-24
影响因子:
5.6
通讯作者:
--
中科院分区:
生物学2区
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一个六亚单位的ATPase环在生命的所有领域形成复制叉子的中心枢纽。该环执行解旋酶功能,以分离要复制的两条互补的DNA链,并沿DNA驱动复制机制。这种解旋酶/ATPase环的破坏与遗传不稳定和癌症等疾病有关。真核生物和古生物的解旋酶/ATPase环由6个微染色体维持(MCM)蛋白组成。先前的结构研究表明,MCM环在螺旋楼梯上结合了一条被包围的DNA链,这表明该环以一种手到手的机制将这条DNA链通过其中央孔拉出,其中楼梯底部的亚单位与DNA解离,并在楼梯上方一步重新结合DNA。用高分辨率冷冻电子显微镜,我们证明了古生物Saccharolobus solfararicus的MCM环以两种不同的方式与环状DNA链结合,结合了不同数量的亚基与DNA,说明了DNA易位过程中DNA解离和重新结合的交替步骤的可能机制。
A six-subunit ATPase ring forms the central hub of the replication forks in all domains of life. This ring performs a helicase function to separate the two complementary DNA strands to be replicated and drives the replication machinery along the DNA. Disruption of this helicase/ATPase ring is associated with genetic instability and diseases such as cancer. The helicase/ATPase rings of eukaryotes and archaea consist of six minichromosome maintenance (MCM) proteins. Prior structural studies have shown that MCM rings bind one encircled strand of DNA in a spiral staircase, suggesting that the ring pulls this strand of DNA through its central pore in a hand-over-hand mechanism where the subunit at the bottom of the staircase dissociates from DNA and re-binds DNA one step above the staircase. With high-resolution cryo-EM, we show that the MCM ring of the archaeal organism Saccharolobus solfataricus binds an encircled DNA strand in two different modes with different numbers of subunits engaged to DNA, illustrating a plausible mechanism for the alternating steps of DNA dissociation and re-association that occur during DNA translocation.
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