Unraveling Important Constraints on the Mechanisms for Redox Signaling in DNA Replication and Repair

Agostino Migliore, Darius Teo and additional members of the Beratan Lab, with collaborators at USC, take an important step towards understanding intracellular redox signaling at the core of DNA repair and replication processes. Experiments suggesting a role for DNA charge transport in mediating such signaling have been the subject of a heated debated in recent literature. The lab has demonstrated that charge transfer between a [4Fe4S] protein and a nucleic acid duplex is unidirectional. This finding implies that exclusive mediation of the iron-sulfur protein signaling by DNA charge transport is kinetically unfeasible, while redox agents in the cell may assist the signaling. Their analysis narrows the range of possible DNA charge transfer-based mechanisms for intracellular signaling, with potential far-reaching implications for future research on drug targets in cancer signaling pathways.  The CellPress journal, Chem, has more on Teo and Migliore's findings here.