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February 23, 2017

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

ScienceNOW - Fetched: February 23rd, 2017, 3:00pm UTC
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. Authors: Elizabeth O’Brien, Marilyn E. Holt, Matthew K. Thompson, Lauren E. Salay, Aaron C. Ehlinger, Walter J. Chazin, Jacqueline K. Barton

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