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Published April 30, 2014 | Published + Supplemental Material
Journal Article Open

DNA-Mediated Signaling by Proteins with 4Fe−4S Clusters Is Necessary for Genomic Integrity


Iron–sulfur clusters have increasingly been found to be associated with enzymes involved in DNA processing. Here we describe a role for these redox clusters in DNA-mediated charge-transport signaling in E. coli between DNA repair proteins from distinct pathways. DNA-modified electrochemistry shows that the 4Fe–4S cluster of DNA-bound DinG, an ATP-dependent helicase that repairs R-loops, is redox-active at cellular potentials and ATP hydrolysis increases DNA-mediated redox signaling. Atomic force microscopy experiments demonstrate that DinG and Endonuclease III (EndoIII), a base excision repair enzyme, cooperate at long-range using DNA charge transport to redistribute to regions of DNA damage. Genetics experiments, moreover, reveal that this DNA-mediated signaling among proteins also occurs within the cell and, remarkably, is required for cellular viability under conditions of stress. Silencing the gene encoding EndoIII in a strain of E. coli where repair by DinG is essential results in a significant growth defect that is rescued by complementation with EndoIII but not with an EndoIII mutant that is enzymatically active but unable to carry out DNA charge transport. This work thus elucidates a fundamental mechanism to coordinate the activities of DNA repair enzymes across the genome.

Additional Information

© 2014 American Chemical Society. ACS AuthorChoice. Received: February 25, 2014. Publication Date (Web): April 16, 2014. We are grateful to the NIH (GM49216), the Moore Foundation (Caltech Signaling Center), and the Center for Environmental Microbial Interactions (CEMI, Caltech) for their financial support. M.A.G. and H.M.S. were NIH predoctoral trainees (NIH/NRSA 5T32GM07616) and T.J.Z. an NSF fellow (DGE-1144469). We are also grateful to the Beckman Institute MMRC for AFM instrumentation. We thank Dr. Huangen Ding (Louisiana State University, Baton Rouge, LA) for helpful discussions regarding DinG, the Coli Genetic Stock Center (CGSC, Yale) for distributing the BW16847 and JW1625-1, and Dr. B. Michel (Gif-sur-Yvette) for the gift of the InvA bacterial strain and RNaseH overexpression plasmid. Lastly we thank Ms. Janani Comar for research assistance. The authors declare no competing financial interest.

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Published - ja501973c.pdf

Supplemental Material - ja501973c_si_001.pdf


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August 20, 2023
August 20, 2023