Cancer-associated SF3B1 mutation suppresses DNA repair by disrupting the organization of nuclear actin network

  • Cell Death Dis. 2026 Mar 21;17(1):334. doi: 10.1038/s41419-026-08569-5.
Rui Qian  1  2 ,  Zhipeng Zhao  3 ,  Xuanxuan Sun  1 ,  Benkai Xin  1 ,  Peipei An  1  2 ,  Ting Yang  1 ,  Ning Wu  3 ,  Xin Hu  2  4 ,  Youzhong Wan  5  6
Affiliations
  • 1. Cancer Biology Laboratory, China-Japan Union Hospital of Jilin University, Jilin University, Changchun, China.
  • 2. Jilin Provincial Key Laboratory of Cancer Biology, Changchun, China.
  • 3. Department of Radiation Oncology, China-Japan Union Hospital of Jilin University, Jilin University, Changchun, China.
  • 4. Department of Cardiology, China-Japan Union Hospital of Jilin University, Jilin University, Changchun, China.
  • 5. Cancer Biology Laboratory, China-Japan Union Hospital of Jilin University, Jilin University, Changchun, China. [email protected].
  • 6. Jilin Provincial Key Laboratory of Cancer Biology, Changchun, China. [email protected].
PMID: 41864997 DOI: 10.1038/s41419-026-08569-5
Abstract

Nuclear Actin filament is required for efficient repair of DNA double-strand breaks. While cancer-associated SF3B1 mutation leads to impaired DNA repair, the underlying mechanism remains elusive. Here, we found that SF3B1 mutation led to defective nuclear Actin network during DNA repair. Mechanistically, SF3B1 mutation increased the expression of circATP9B, which interacted with and facilitated the degradation of MYH9. MYH9 deficiency abolished the assembly of nuclear Actin network, which, in turn, suppressed the movement and clustering of DNA damage foci, resulting in inefficient DNA repair. Together, our study reveals a novel mechanism by which SF3B1 mutation influences Cancer progression via circRNA, and underscores the important role of MYH9 in organization of nuclear Actin network.

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