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Updated: May 28, 2026
10:24
Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
Published on: September 28, 2012
The ubiquitin-selective segregase VCP/p97 orchestrates the response to DNA double-strand breaks
Mayura Meerang1, Danilo Ritz, Shreya Paliwal
1Institute of Pharmacology and Toxicology, University of Zürich-Vetsuisse, Winterthurerstrasse 260, 8057 Zürich, Switzerland.
Nature Cell Biology
|October 25, 2011
Summary
The p97-UFD1-NPL4 complex is vital for DNA double-strand break (DSB) repair by removing ubiquitin chains, ensuring genome stability after radiation exposure.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Unrepaired DNA double-strand breaks (DSBs) lead to genetic instability and cell death.
- Ubiquitin modification is crucial for DNA damage signaling, but its role in complex assembly is unclear.
Purpose of the Study:
- To investigate the role of the p97-UFD1-NPL4 complex in DNA double-strand break repair.
- To elucidate how ubiquitylation coordinates the assembly of DNA repair signaling complexes.
Main Methods:
- Investigated the interaction between p97 (VCP) and RNF8 in response to ionizing radiation.
- Analyzed the recruitment of p97 to DNA lesions via UFD1-NPL4 and Lys-48-linked ubiquitin (K48-Ub) chains.
- Assessed the impact of p97 activity on the association of 53BP1, BRCA1, and RAD51.
Main Results:
- p97 cooperates with RNF8 to orchestrate signaling complex assembly and DSB repair.
- p97 is recruited to DNA lesions by UFD1-NPL4 and K48-Ub chains, regulated by RNF8.
- p97 removes K48-Ub conjugates, facilitating the proper association of 53BP1, BRCA1, and RAD51 for DNA repair.
Conclusions:
- The p97-UFD1-NPL4 complex is essential for ubiquitin-mediated DNA damage response.
- This complex plays a critical role in maintaining genome stability by ensuring efficient DSB repair.
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