2. Academic Validation
  3. Phosphorylated Y14 condensates as a scaffold for DNA double-strand break repair

Phosphorylated Y14 condensates as a scaffold for DNA double-strand break repair

  • iScience. 2025 Jul 7;28(8):113073. doi: 10.1016/j.isci.2025.113073.
Chun-Hao Su 1,  Tzu-Wei Chuang 1,  Hsin-Hong Yeh 1,  Chiu-Lun Shen 1,  Pei-Yu Hung 1 2,  Ying Li 3,  Woan-Yuh Tarn 1
Affiliations

Affiliations

  • 1 Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
  • 2 Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 100233, Taiwan.
  • 3 Department of Chemistry, University of Hong Kong, Hong Kong 999077, China.
PMID: 40727937 DOI: 10.1016/j.isci.2025.113073
Abstract

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.

Keywords

biochemistry; molecular biology.

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