Phosphorylated Y14 condensates as a scaffold for DNA double-strand break repair
Summary: Various DNA damage response factors form biomolecular condensates at DNA lesions. Targeting phase separation in DNA repair factor assemblies may provide a potential anticancer strategy. An RNA-binding protein, Y14/RBM8A, facilitates the repair of DNA double-strand breaks (DSBs) via its RNA-...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-08-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225013343 |
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| author | Chun-Hao Su Tzu-Wei Chuang Hsin-Hong Yeh Chiu-Lun Shen Pei-Yu Hung Ying Li Woan-Yuh Tarn |
| author_facet | Chun-Hao Su Tzu-Wei Chuang Hsin-Hong Yeh Chiu-Lun Shen Pei-Yu Hung Ying Li Woan-Yuh Tarn |
| author_sort | Chun-Hao Su |
| collection | DOAJ |
| description | Summary: Various DNA damage response factors form biomolecular condensates at DNA lesions. Targeting phase separation in DNA repair factor assemblies may provide a potential anticancer strategy. An RNA-binding protein, Y14/RBM8A, facilitates the repair of DNA double-strand breaks (DSBs) via its RNA-mediated interaction with non-homologous end joining (NHEJ) factors. HaloTag-Y14 fusion is distributed to laser-induced DNA damage sites in an RNA-dependent manner. Serine/arginine (SR) protein kinase 1-mediated phosphorylation of Y14 was also crucial for its localization at DNA lesions and function in DSB repair. Magnesium promoted liquid-liquid phase separation of phosphorylated Y14 in vitro. Ku70/80 could partition into phosphorylated Y14 condensates. Chelation of divalent cations abolished Y14 localization and subsequent recruitment of NHEJ factors at DNA damage sites. Inhibition of Y14 phosphorylation interfered with Ku70/80 recruitment and increased the sensitivity of cancer cells to DNA damage. This study reinforces that manipulating DNA repair foci can improve the efficacy of anticancer agents. |
| format | Article |
| id | doaj-art-a20932f27b92445d9b22e9b833d022f4 |
| institution | OA Journals |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-a20932f27b92445d9b22e9b833d022f42025-08-20T02:38:52ZengElsevieriScience2589-00422025-08-0128811307310.1016/j.isci.2025.113073Phosphorylated Y14 condensates as a scaffold for DNA double-strand break repairChun-Hao Su0Tzu-Wei Chuang1Hsin-Hong Yeh2Chiu-Lun Shen3Pei-Yu Hung4Ying Li5Woan-Yuh Tarn6Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei 11529, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei 11529, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei 11529, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 100233, TaiwanDepartment of Chemistry, University of Hong Kong, Hong Kong 999077, ChinaInstitute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Corresponding authorSummary: Various DNA damage response factors form biomolecular condensates at DNA lesions. Targeting phase separation in DNA repair factor assemblies may provide a potential anticancer strategy. An RNA-binding protein, Y14/RBM8A, facilitates the repair of DNA double-strand breaks (DSBs) via its RNA-mediated interaction with non-homologous end joining (NHEJ) factors. HaloTag-Y14 fusion is distributed to laser-induced DNA damage sites in an RNA-dependent manner. Serine/arginine (SR) protein kinase 1-mediated phosphorylation of Y14 was also crucial for its localization at DNA lesions and function in DSB repair. Magnesium promoted liquid-liquid phase separation of phosphorylated Y14 in vitro. Ku70/80 could partition into phosphorylated Y14 condensates. Chelation of divalent cations abolished Y14 localization and subsequent recruitment of NHEJ factors at DNA damage sites. Inhibition of Y14 phosphorylation interfered with Ku70/80 recruitment and increased the sensitivity of cancer cells to DNA damage. This study reinforces that manipulating DNA repair foci can improve the efficacy of anticancer agents.http://www.sciencedirect.com/science/article/pii/S2589004225013343biochemistrymolecular biology |
| spellingShingle | Chun-Hao Su Tzu-Wei Chuang Hsin-Hong Yeh Chiu-Lun Shen Pei-Yu Hung Ying Li Woan-Yuh Tarn Phosphorylated Y14 condensates as a scaffold for DNA double-strand break repair iScience biochemistry molecular biology |
| title | Phosphorylated Y14 condensates as a scaffold for DNA double-strand break repair |
| title_full | Phosphorylated Y14 condensates as a scaffold for DNA double-strand break repair |
| title_fullStr | Phosphorylated Y14 condensates as a scaffold for DNA double-strand break repair |
| title_full_unstemmed | Phosphorylated Y14 condensates as a scaffold for DNA double-strand break repair |
| title_short | Phosphorylated Y14 condensates as a scaffold for DNA double-strand break repair |
| title_sort | phosphorylated y14 condensates as a scaffold for dna double strand break repair |
| topic | biochemistry molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225013343 |
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