The [4Fe4S] cluster of human DNA primase functions as a redox switch using DNA charge transport.

Elizabeth O'Brien, Marilyn E Holt, Matthew K Thompson, Lauren E Salay, Aaron C Ehlinger, Walter J Chazin, Jacqueline K Barton

Science (New York, N.Y.) 2017 Feb 24

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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. Copyright © 2017, American Association for the Advancement of Science.

Citation

Elizabeth O'Brien, Marilyn E Holt, Matthew K Thompson, Lauren E Salay, Aaron C Ehlinger, Walter J Chazin, Jacqueline K Barton. 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)