ArticleNucleic acids research2023
RAP80 phase separation at DNA double-strand break promotes BRCA1 recruitment.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 24 citations in OpenAlex.
- Deacetylase-independent HDAC1 condensation defines temozolomide response in glioblastoma.Nature chemical biology · 2026Article
- USP7 at PML Nuclear Bodies: A Protein Interaction Network Perspective.International journal of molecular sciences · 2026Article
- Targeted inhibition of the CREB1-CtIP axis enhances the efficacy of abiraterone combined with radiotherapy in prostate cancer.Cell death & disease · 2026Article
- CBX2 phase-separation contributes to homologous recombination repair and drug resistance in ovarian cancer.Cell death & disease · 2026Article
- Distinct mechanisms of recognition of phosphorylated RNAPII C-terminal domain by BRCT repeats of the BRCA1-BARD1 complex.The Journal of biological chemistry · 2026Article
- Liquid-Liquid Phase Separation in Cancer Drug Resistance: Mechanisms and Therapeutic Opportunities.Oncology research · 2026Review
- Complexes Formed by the K63-Specific Deubiquitinating Enzyme BRCC36: New Promising Therapeutic Targets in Human Disease.Biomolecules · 2025Review
- Molecular mechanisms mediated by liquid-liquid phase separation in chronic liver disease progression.iScience · 2025Review
- Nuclear and genome dynamics underlying DNA double-strand break repair.Nature reviews. Molecular cell biology · 2025Review
- Off-pore Nup98 condensates mobilize heterochromatic breaks and exclude Rad51.Molecular cell · 2025Article
- Current perspectives in drug targeting intrinsically disordered proteins and biomolecular condensates.BMC biology · 2025Review
- CDK1-mediated phosphorylation of USP37 regulates SND1 stability and promotes oncogenesis in colorectal cancer.Acta pharmaceutica Sinica. B · 2025Article
- Protein quality control machinery: regulators of condensate architecture and functionality.Trends in biochemical sciences · 2025Review
- Liquid-liquid phase separation-driven molecular subtyping and prognostic modeling in colorectal cancer.Frontiers in immunology · 2025Article
- Phase separation in DNA repair: orchestrating the cellular response to genomic stability.PeerJ · 2025Review
- The strand exchange domain of tumor suppressor PALB2 is intrinsically disordered and promotes oligomerization-dependent DNA compaction.iScience · 2024Article
- Review
- "Off-pore" nucleoporins relocalize heterochromatic breaks through phase separation.bioRxiv : the preprint server for biology · 2024Article
- Ubiquitin-induced RNF168 condensation promotes DNA double-strand break repair.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Liquid-liquid phase separation in diseases.MedComm · 2024Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
RAP80 has been characterized as a component of the BRCA1-A complex and is responsible for the recruitment of BRCA1 to DNA double-strand breaks (DSBs). However, we and others found that the recruitment of RAP80 and BRCA1 were not absolutely temporally synchronized, indicating that other mechanisms, apart from physical interaction, might be implicated. Recently, liquid-liquid phase separation (LLPS) has been characterized as a novel mechanism for the organization of key signaling molecules to drive their particular cellular functions. Here, we characterized that RAP80 LLPS at DSB was required for RAP80-mediated BRCA1 recruitment. Both cellular and in vitro experiments showed that RAP80 phase separated at DSB, which was ascribed to a highly disordered region (IDR) at its N-terminal. Meanwhile, the Lys63-linked poly-ubiquitin chains that quickly formed after DSBs occur, strongly enhanced RAP80 phase separation and were responsible for the induction of RAP80 condensation at the DSB site. Most importantly, abolishing the condensation of RAP80 significantly suppressed the formation of BRCA1 foci, encovering a pivotal role of RAP80 condensates in BRCA1 recruitment and radiosensitivity. Together, our study disclosed a new mechanism underlying RAP80-mediated BRCA1 recruitment, which provided new insight into the role of phase separation in DSB repair.
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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.