1. The RING Finger Protein RNF8 Ubiquitinates Nbs1 to Promote DNA Double-strand Break Repair by Homologous Recombination*
- Author
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Lu, Chi-Sheng, Truong, Lan N, Aslanian, Aaron, Shi, Linda Z, Li, Yongjiang, Hwang, Patty Yi-Hwa, Koh, Kwi Hye, Hunter, Tony, Yates, John R, Berns, Michael W, and Wu, Xiaohua
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Genetics ,Underpinning research ,1.1 Normal biological development and functioning ,Generic health relevance ,Cell Cycle Proteins ,Cell Line ,Tumor ,DNA Breaks ,Double-Stranded ,DNA Repair ,DNA-Binding Proteins ,Homologous Recombination ,Humans ,Lasers ,Nuclear Proteins ,Ubiquitin-Protein Ligases ,Ubiquitination ,Chemical Sciences ,Medical and Health Sciences ,Biochemistry & Molecular Biology ,Biological sciences ,Biomedical and clinical sciences ,Chemical sciences - Abstract
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.
- Published
- 2012