Redox Signaling through DNA
Biological electron transfer reactions between metal cofactors are critical to many essential processes within the cell. Duplex DNA is, moreover, capable of mediating the transport of charge through its π-stacked nitrogenous bases. Increasingly, [4Fe4S] clusters, generally redox-active cofactors, have been found to be associated with enzymes involved in DNA processing. DNA-binding enzymes containing [4Fe4S] clusters can thus utilize DNA charge transport (DNA CT) for redox signaling to coordinate reactions over long molecular distances. In particular, DNA CT signaling may represent the first step in the search for DNA lesions by proteins containing [4Fe4S] clusters that are involved in DNA repair. Here we describe research carried out to examine the chemical characteristics and biological consequences of DNA CT. We are finding that DNA CT among metalloproteins represents powerful chemistry for redox signaling at long range within the cell.
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Issue online: 4 October 2016; Version of record online: 29 July 2016; Manuscript Received: 1 April 2016. We are grateful to our many coworkers and collaborators for their contributions to this research. We are also especially grateful to our colleague, Harry Gray, for many insights, both respect to protein electron transfer and beyond! E. O. B. thanks the NIH for training and R. M. B. S. thanks the NSF for fellowship support. We are also grateful to the NIH (GM61077) and the Moore foundation for their financial support.
Accepted Version - nihms837715.pdf