Login / Signup

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

Elizabeth O'BrienMarilyn E HoltMatthew K ThompsonLauren E SalayAaron C EhlingerWalter Jacob ChazinJacqueline K Barton
Published in: Science (New York, N.Y.) (2017)
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.
Keyphrases
  • circulating tumor
  • cell free
  • single molecule
  • endothelial cells
  • dna binding
  • circulating tumor cells
  • transcription factor
  • metal organic framework
  • drug discovery