The RING Finger Protein RNF8 Ubiquitinates Nbs1 to Promote DNA Double-strand Break Repair by Homologous Recombination
Copyright policy )The RING Finger Protein RNF8 Ubiquitinates Nbs1 to Promote DNA Double-strand Break Repair by Homologous Recombination
Ubiquitination plays an important role in the DNA damage response. We identified a novel interaction of the E3 ubiquitin ligase RNF8 with Nbs1, a key regulator of DNA double-strand break (DSB) repair. We found that Nbs1 is ubiquitinated both before and after DNA damage and is a direct ubiquitination substrate of RNF8. We also identified key residues on Nbs1 that are ubiquitinated by RNF8. By using laser microirradiation and live-cell imaging, we observed that RNF8 and its ubiquitination activity are important for promoting optimal binding of Nbs1 to DSB-containing chromatin. We also demonstrated that RNF8-mediated ubiquitination of Nbs1 contributes to the efficient and stable binding of Nbs1 to DSBs and is important for HR-mediated DSB repair. Taken together, these studies suggest that Nbs1 is one important target of RNF8 to regulate DNA DSB repair.
- Scripps Research Institute United States
- University of California, San Diego United States
- Salk Institute for Biological Studies United States
- University of California, San Francisco United States
570, Biochemistry & Molecular Biology, Biomedical and clinical sciences, DNA Repair, 1.1 Normal biological development and functioning, Ubiquitin-Protein Ligases, Cell Cycle Proteins, Medical and Health Sciences, Cell Line, Double-Stranded, Cell Line, Tumor, Genetics, Humans, DNA Breaks, Double-Stranded, Homologous Recombination, Cancer, Tumor, Lasers, DNA Breaks, Ubiquitination, Nuclear Proteins, Biological Sciences, DNA-Binding Proteins, Biological sciences, Chemical sciences, Chemical Sciences, Biochemistry and Cell Biology, Generic health relevance
570, Biochemistry & Molecular Biology, Biomedical and clinical sciences, DNA Repair, 1.1 Normal biological development and functioning, Ubiquitin-Protein Ligases, Cell Cycle Proteins, Medical and Health Sciences, Cell Line, Double-Stranded, Cell Line, Tumor, Genetics, Humans, DNA Breaks, Double-Stranded, Homologous Recombination, Cancer, Tumor, Lasers, DNA Breaks, Ubiquitination, Nuclear Proteins, Biological Sciences, DNA-Binding Proteins, Biological sciences, Chemical sciences, Chemical Sciences, Biochemistry and Cell Biology, Generic health relevance
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