DNA repair glycosylases with a [4Fe–4S] cluster: A redox cofactor for DNA-mediated charge transport?
The [4Fe–4S] cluster is ubiquitous to a class of base excision repair enzymes in organisms ranging from bacteria to man and was first considered as a structural element, owing to its redox stability under physiological conditions. When studied bound to DNA, two of these repair proteins (MutY and Endonuclease III from Escherichia coli) display DNA-dependent reversible electron transfer with characteristics typical of high potential iron proteins. These results have inspired a reexamination of the role of the [4Fe–4S] cluster in this class of enzymes. Might the [4Fe–4S] cluster be used as a redox cofactor to search for damaged sites using DNA-mediated charge transport, a process well known to be highly sensitive to lesions and mismatched bases? Described here are experiments demonstrating the utility of DNA-mediated charge transport in characterizing these DNA-binding metalloproteins, as well as efforts to elucidate this new function for DNA as an electronic signaling medium among the proteins.
© 2007 Elsevier Inc. Received 9 March 2007; received in revised form 30 April 2007; accepted 3 May 2007. Available online 17 May 2007. In memory of Edward I. Stiefel. We are grateful to the NIH (GM49216) for their financial support. We also thank our coworkers and collaborators for their efforts, and we are grateful to Ed Stiefel for getting one of us (J.K.B.) excited about Fe–S clusters at the beginning.
Accepted Version - nihms33826.pdf