The RING Finger Protein RNF8 Ubiquitinates Nbs1 to Promote DNA Double-strand Break Repair by Homologous Recombination |
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| Authors: | Chi-Sheng Lu Lan N. Truong Aaron Aslanian Linda Z. Shi Yongjiang Li Patty Yi-Hwa Hwang Kwi Hye Koh Tony Hunter John R. Yates III Michael W. Berns Xiaohua Wu |
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| Affiliation: | From the ‡Department of Molecular and Experimental Medicine and ;the ¶Department of Chemical Physiology, Scripps Research Institute, La Jolla, California 92037.;the §Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037.;the ‖Institute of Engineering in Medicine, University of California at San Diego, La Jolla, California 92093 |
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| 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. |
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| Keywords: | DNA Damage Response DNA Repair Homologous Recombination Post-translational Modification Ubiquitination Double Strand Break (DSB) Repair Nbs1 RNF8 |
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