A Redox Role for the [4Fe4S] Cluster of Yeast DNA Polymerase δ

Phillip L. Bartels, Joseph L. Stodola, Peter M.J. Burgers, Jacqueline K. Barton

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

A [4Fe4S]2+ cluster in the C-terminal domain of the catalytic subunit of the eukaryotic B-family DNA polymerases is essential for the formation of active multi-subunit complexes. Here we use a combination of electrochemical and biochemical methods to assess the redox activity of the [4Fe4S]2+ cluster in Saccharomyces cerevisiae polymerase (Pol) δ, the lagging strand DNA polymerase. We find that Pol δ bound to DNA is indeed redox-active at physiological potentials, generating a DNA-mediated signal electrochemically with a midpoint potential of 113 ± 5 mV versus NHE. Moreover, biochemical assays following electrochemical oxidation of Pol δ reveal a significant slowing of DNA synthesis that can be fully reversed by reduction of the oxidized form. A similar result is apparent with photooxidation using a DNA-tethered anthraquinone. These results demonstrate that the [4Fe4S] cluster in Pol δ can act as a redox switch for activity, and we propose that this switch can provide a rapid and reversible way to respond to replication stress.

Original languageEnglish
Pages (from-to)18339-18348
Number of pages10
JournalJournal of the American Chemical Society
Volume139
Issue number50
DOIs
StatePublished - Dec 20 2017

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