DNA-mediated redox signaling for transcriptional activation of SoxR
In enteric bacteria, the cellular response to oxidative stress is activated by oxidation of the iron-sulfur clusters in SoxR, which then induces transcription of soxS, turning on a battery of defense genes. Here we demonstrate both in vitro and in cells that activation of SoxR can occur in a DNA-mediated reaction with guanine radicals, an early genomic signal of oxidative stress, serving as the oxidant. SoxR in its reduced form is found to inhibit guanine damage by repairing guanine radicals. Moreover, cells treated with a DNA-binding photooxidant, which generates guanine radicals, promotes the expression of soxS. In vitro, this photooxidant, tethered to DNA 80 bp from the soxS promoter, induces transcription by activating SoxR upon irradiation. Thus, transcription can be activated from a distance through DNA-mediated charge transport. This chemistry offers a general strategy for DNA-mediated signaling of oxidative stress.
Copyright ©2009 by the National Academy of Sciences. Contributed by Jacqueline K. Barton, June 10, 2009 (received for review May 15, 2009). Published online before print July 27, 2009, doi: 10.1073/pnas.0906429106 We thank the National Institutes of Health (NIH) (GM49216 to J.K.B. and CA37831 to B.D.) for their financial support of this research. We thank also Dr. Eunsuk Kim and Dr. Lars Dietrich for their preparations of E. coli and P. Aeruginosa SoxR, respectively. Author contributions: B.D. and J.K.B. designed research; P.E.L. performed research; P.E.L. analyzed data; and P.E.L. and J.K.B. wrote the paper. The authors declare no conflict of interest.
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