DNA-Mediated Signaling by Proteins with 4Fe−4S Clusters Is Necessary for Genomic Integrity
| Autor: | Helen M. Segal, Theodore J. Zwang, Michael A. Grodick, Jacqueline K. Barton |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
DNA
Bacterial Iron-Sulfur Proteins DNA Repair DNA repair DNA damage Mutant 010402 general chemistry 01 natural sciences Biochemistry Article Catalysis DNA Glycosylases Deoxyribonuclease (Pyrimidine Dimer) 03 medical and health sciences chemistry.chemical_compound Colloid and Surface Chemistry Bacterial Proteins Escherichia coli 030304 developmental biology 0303 health sciences biology Escherichia coli Proteins Helicase General Chemistry Base excision repair 0104 chemical sciences chemistry DNA glycosylase biology.protein Oxidation-Reduction Gene Deletion DNA Signal Transduction Nucleotide excision repair |
| Zdroj: | Journal of the American Chemical Society |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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