Electron transfer and DNA replication: Assessing the functional role of the yeast DNA polymerase δ [4Fe- 4S] 2+ cluster
Eukaryotic B- family DNA polymerases have recently been shown to contain a conserved [4Fe- 4S]2+ cluster in the C- terminus of the catalytic subunit. This cofactor has been most completely characterized in yeast DNA polymerase δ (Pol δ) , the enzyme responsible for lagging strand DNA synthesis. Multiple lines of evidence point to a role for the cluster beyond structural integrity, but the nature of this function is not obvious. Clues to what this function might be come from previous work in the Barton lab, which showed that [4Fe- 4S]2+ clusters in bacterial base excision repair enzymes undergo a shift in potential favoring oxidn. upon binding to DNA, allowing them to utilize DNA- mediated redox signaling to coordinate their activities and find their targets. Building on this earlier work, we have investigated the capability of the Pol δ [4Fe- 4S]2+ cluster to undergo reversible electron transfer using DNA- modified electrodes, and have designed assays to test the effect of redox state on enzymic activity.
© 2015 American Chemical Society.