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Published on: April 21, 2023
SENP3 regulates DNA damage repair by downregulating RAP80 SUMOylation
Jianfeng Fu1,2, Min Wei1,2, Ruidan Xu1,2
1State Key Laboratory of Gene Function and Modulation Research, School of Life Sciences, Peking University, Beijing 100871, China.
Acta Biochimica Et Biophysica Sinica
|May 7, 2026
Summary
SENP3 regulates DNA repair by controlling Receptor-associated protein 80 (RAP80) SUMOylation and dissociation from DNA damage sites. This dynamic control is crucial for homologous recombination repair and cellular response to DNA damage.
Area of Science:
- Molecular Biology
- Cellular Biology
- Genetics
Background:
- Receptor-associated protein 80 (RAP80) is vital for the BRCA1-A complex in DNA double-strand break (DSB) repair via homologous recombination (HR).
- Post-translational modifications (PTMs) regulate RAP80 function, but detailed mechanisms are unclear.
Purpose of the Study:
- To investigate the role of SENP3 in regulating DNA damage repair by targeting RAP80.
- To elucidate the mechanistic interplay between SENP3, RAP80, and the BRCA1-A complex during DSB repair.
Main Methods:
- Investigated the dynamic regulation of RAP80 by SENP3 in response to DNA damage.
- Utilized techniques to assess SUMOylation, recruitment to DSB sites, and dissociation of RAP80.
- Examined the impact of SENP3 depletion on HR repair and cellular sensitivity to genotoxic agents.
Main Results:
- SENP3 dynamically regulates DSB repair by targeting RAP80.
- Upon DNA damage, RAP80 SUMOylation facilitates its recruitment to DSB sites, promoting BRCA1 recruitment.
- SENP3 promotes RAP80 dissociation from DNA damage sites, ensuring timely repair progression and termination of the DNA damage response.
- SENP3 depletion impairs HR repair and increases sensitivity to irradiation and chemotherapy.
Conclusions:
- SENP3 is a key regulator of DNA repair.
- SENP3 controls RAP80-BRCA1 complex formation and dissociation, impacting DNA damage response dynamics.
- Targeting SENP3-mediated regulation of RAP80 offers potential therapeutic strategies for DNA repair deficiencies.
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