title: DNA-mediated signaling by proteins with 4Fe-4S clusters is necessary for genomic integrity.
abstract: 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.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology , Pasadena, California 91125, United States.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Grodick
authors.forename: Helen M
authors.initials: HM
authors.lastname: Segal
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Zwang
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Barton
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D045647:DNA Glycosylases / Q000378:metabolism; D004260:DNA Repair; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism*; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D007506:Iron-Sulfur Proteins; C074432:dinG protein, E coli; C075518:invA protein, Bacteria; D043224:Deoxyribonuclease (Pyrimidine Dimer); C106403:NTH protein, E coli; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase
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