The RING Finger Protein RNF8 Ubiquitinates Nbs1 to Promote DNA Double-strand Break Repair by Homologous Recombination*

Background: The Mre11-Rad50-Nbs1 (MRN) complex and the ubiquitin E3 ligase RNF8 play important roles in DNA DSB repair. Results: RNF8 interacts with and ubiquitinates Nbs1 to promote binding of Nbs1 to DSBs and HR-mediated DSB repair. Conclusion: Nbs1 ubiquitination by RNF8 is important for Nbs1 recruitment to DSBs and HR-mediated repair of DSBs. Significance: These studies help to understand how ubiquitination modifications contribute to DSB repair and genome stability maintenance in mammalian cells. 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.

• Publication year

  2012

• Venue

  Journal of Biological Chemistry

• Publication date

  2012-10-31

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.M112.421545PMID 23115235PMCID PMC3527981
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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