2. Academic Validation
  3. The m6A reader IGF2BP2 promotes homologous recombination-mediated DNA repair by eliminating DNA-RNA hybrids

The m6A reader IGF2BP2 promotes homologous recombination-mediated DNA repair by eliminating DNA-RNA hybrids

  • Cell Rep. 2025 Oct 28;44(10):116438. doi: 10.1016/j.celrep.2025.116438.
Yating Sun 1,  Haojie Zhang 2,  Shiwei Li 3,  Jinzhi Zhang 4,  Bin Lyu 4,  Liping Kang 4,  Xinkun Teng 4,  Mingwei Yin 5,  Weidong Peng 6,  Jingjing Wang 4,  Zhimin Chu 4,  Chengying Cui 4,  Dejie Kong 4,  Mingqing Wu 4,  Yongqiang Wang 7,  Jiadong Wang 8,  Yang Li 9
Affiliations

Affiliations

  • 1 Department of Genetics, School of Life Science, Anhui Medical University, Hefei, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University International Cancer Institute, Institute of Advanced Clinical Medicine, State Key Laboratory of Molecular Oncology, Peking University Health Science Center, Beijing 100191, China.
  • 2 Department of Urology, Huadong Hospital, Fudan University, Shanghai, China.
  • 3 Department of Radiation Medicine, School of Basic Medical Sciences, Peking University International Cancer Institute, Institute of Advanced Clinical Medicine, State Key Laboratory of Molecular Oncology, Peking University Health Science Center, Beijing 100191, China.
  • 4 Department of Genetics, School of Life Science, Anhui Medical University, Hefei, China.
  • 5 Department of Pathophysiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
  • 6 Department of Genetics, School of Life Science, Anhui Medical University, Hefei, China; Department of Pathology, The Second Hospital of Anhui Medical University, Hefei, China.
  • 7 Department of Urology, South China Hospital, Medical School, Shenzhen University, Shenzhen, China. Electronic address: [email protected].
  • 8 Department of Radiation Medicine, School of Basic Medical Sciences, Peking University International Cancer Institute, Institute of Advanced Clinical Medicine, State Key Laboratory of Molecular Oncology, Peking University Health Science Center, Beijing 100191, China. Electronic address: [email protected].
  • 9 Department of Genetics, School of Life Science, Anhui Medical University, Hefei, China; Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Hefei, China. Electronic address: [email protected].
PMID: 41100254 DOI: 10.1016/j.celrep.2025.116438
Abstract

Double-strand breaks (DSBs) are among the most deleterious forms of DNA damage and are precisely repaired through homologous recombination (HR). DNA-RNA hybrids formed at DSB sites play a critical role in HR-mediated repair and must be tightly regulated. Here, we identify the m6A reader IGF2BP2, together with the RNA helicase DHX9, as key factors recruited to DSBs that remove DNA-RNA hybrids in an m6A-dependent manner. This axis prevents hybrid accumulation, enables RAD51 loading, and promotes HR-mediated repair. Loss of IGF2BP2 sensitizes Cancer cells and xenograft tumors to DNA damage-inducing therapies, revealing therapeutic implications.

Keywords

CP: Molecular biology; DHX9; DNA repair; DNA-RNA hybrids; IGF2BP2; RAD51; cancer therapy; homologous recombination; m(6)A modification.

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