- O'Brien E, Holt ME, Thompson MK, Salay LE, Ehlinger AC, Chazin WJ, Barton JK. The [4Fe4S] cluster of human DNA primase functions as a redox switch using DNA charge transport. Science (New York, N.Y.). 2017 Feb 24;355(6327). PMID: 28232525 [PubMed].
DNA charge transport chemistry offers a means of long-range, rapid redox signaling. We demonstrate that the [4Fe4S] cluster in human DNA primase can make use of this chemistry to coordinate the first steps of DNA synthesis. Using DNA electrochemistry, we found 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 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.