ArticleGenes & development2016
A phosphorylation-deubiquitination cascade regulates the BRCA2-RAD51 axis in homologous recombination.
Article in Genes & development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 101 citations in OpenAlex.
- Not only as a Cullin3 ligase adaptor, SPOP may also act as a molecular bridge.Genes & diseases · 2027Review
- Balancing Ubiquitination and Deubiquitination in Apoptotic Protein Stability and Cancer Cell Survival.International journal of molecular sciences · 2026Review
- The MAZ-POLD1 Signaling Axis Drives Cisplatin Resistance in Bladder Cancer by Activating DNA Damage Repair.Cancers · 2026Article
- Ubiquitin C-terminal hydrolase L3 promotes liver cancer cell proliferation by modulating the AMP-activated protein kinase signaling pathway.Journal of cancer research and clinical oncology · 2026Article
- The Potential Role of Deubiquitinating Enzymes (DUBs) in Male Fertility.Biomolecules · 2026Review
- ACTG1 promotes breast cancer aggressiveness and confers ribociclib resistance by deubiquitinating HSPA8 through UCHL3.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- USP26-mediated stabilization of RAD51 promotes endometrial cancer progression and limits ferroptosis.Frontiers in oncology · 2026Article
- Developing therapeutic strategies to target MCL1 and BCLXL in lethal prostate cancer.iScience · 2025Article
- UHRF1 Controls the Timing of RAD51 Removal During DNA Damage Repair Through Suppressing RFWD3.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The cytoskeletal protein smoothelin maintains homologous recombination repair by stabilizing RAD51 in an HUWE1-dependent manner in colorectal cancer.Acta pharmaceutica Sinica. B · 2025Article
- Phosphorylation of RNF213 by ATM-mediated ubiquitination of RPA1 regulates homologous recombination repair and chemosensitivity.Cell death & disease · 2025Article
- UCHL3: a crucial deubiquitinase in DNA damage repair and tumor progression.Cancer cell international · 2025Review
- Advancing the Exploration of the Ubiquitin-like Protein FUBI with Synthetic Chemical Tools.Chembiochem : a European journal of chemical biology · 2025Article
- Targeting DNA Damage Response-Mediated Resistance in Non-Small Cell Lung Cancer: From Mechanistic Insights to Drug Development.Current oncology (Toronto, Ont.) · 2025Review
- Post-translational modifications in DNA damage repair: mechanisms underlying temozolomide resistance in glioblastoma.Oncogene · 2025Review
- In silico structural analysis of Oryza sativa RAD51 reveals key interactions for nucleoprotein filament assembly and regulation.PloS one · 2025Article
- SPIN1 accelerates tumorigenesis and confers radioresistance in non-small cell lung cancer by orchestrating the FOXO3a/FOXM1 axis.Cell death & disease · 2024Article
- USP25 Elevates SHLD2-Mediated DNA Double-Strand Break Repair and Regulates Chemoresponse in Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- UCHL3 induces radiation resistance and acquisition of mesenchymal phenotypes by deubiquitinating POLD4 in glioma stem cells.Cellular and molecular life sciences : CMLS · 2024Article
- GSK3β and UCHL3 govern RIPK4 homeostasis via deubiquitination to enhance tumor metastasis in ovarian cancer.Oncogene · 2024Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Homologous recombination (HR) is one of the major DNA double-strand break (DSB) repair pathways in mammalian cells. Defects in HR trigger genomic instability and result in cancer predisposition. The defining step of HR is homologous strand exchange directed by the protein RAD51, which is recruited to DSBs by BRCA2. However, the regulation of the BRCA2-RAD51 axis remains unclear. Here we report that ubiquitination of RAD51 hinders RAD51-BRCA2 interaction, while deubiquitination of RAD51 facilitates RAD51-BRCA2 binding and RAD51 recruitment and thus is critical for proper HR. Mechanistically, in response to DNA damage, the deubiquitinase UCHL3 is phosphorylated and activated by ATM. UCHL3, in turn, deubiquitinates RAD51 and promotes the binding between RAD51 and BRCA2. Overexpression of UCHL3 renders breast cancer cells resistant to radiation and chemotherapy, while depletion of UCHL3 sensitizes cells to these treatments, suggesting a determinant role of UCHL3 in cancer therapy. Overall, we identify UCHL3 as a novel regulator of DNA repair and reveal a model in which a phosphorylation-deubiquitination cascade dynamically regulates the BRCA2-RAD51 pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.