The [4Fe4S] cluster of human DNA primase functions as a redox switch using DNA charge transport.
The [4Fe4S] cluster of human DNA primase functions as a redox switch using DNA charge transport.
复制标题
DOI：
10.1126/science.aag1789
复制
发表时间：
2017-02-24
期刊：
影响因子：
--
通讯作者：
Barton JK
中科院分区：
文献类型：
--
作者：
O'Brien E;Holt ME;Thompson MK;Salay LE;Ehlinger AC;Chazin WJ;Barton JK
DNA电荷传输化学提供了一种远距离、快速氧化还原信号传导的手段。在这里，我们证明了人类DNA引发酶中的[4Fe4S]簇可以利用这种化学来协调复制的第一步。通过DNA电化学，我们发现，在氧化态的[4Fe4S]簇的变化作为一个开关的DNA结合。此外，抑制这种电荷转移的单原子突变会阻碍引发酶的启动，而不会影响引发酶的结构或聚合。在生长的引物双链体中产生单个碱基错配，这减弱了DNA电荷传输，抑制了引物截短。因此，通过[4Fe4S]簇使用DNA电荷传输的氧化还原信号调节引发酶与DNA的结合，并说明了在DNA复制期间可以有效地驱动聚合酶之间的底物传递的化学。DNA引发酶中的[4Fe4S]簇是DNA结合的氧化还原开关，利用DNA电荷传输启动引物合成并促进引物传递。
DNA charge transport chemistry offers a means of long range, rapid redox signaling. Here we demonstrate that the [4Fe4S] cluster in human DNA primase can utilize this chemistry to coordinate the first steps of replication. Through DNA electrochemistry, we find that a change in oxidation state of the [4Fe4S] cluster acts as a switch for DNA binding. Single-atom mutations that inhibit this charge transfer, moreover, hinder primase initiation without affecting primase structure or polymerization. Generating a single base mismatch in the growing primer duplex, which attenuates DNA charge transport, inhibits primer truncation. Thus redox signaling by [4Fe4S] clusters using DNA charge transport regulates primase binding to DNA and illustrates chemistry that may efficiently drive substrate handoff between polymerases during DNA replication. The [4Fe4S] cluster in DNA primase is a redox switch for DNA binding, using DNA charge transport to initiate primer synthesis and facilitate primer handoff.