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TFIP11 promotes replication fork reversal to preserve genome stability

Author

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  • Junliang Chen

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University)

  • Mingjie Wu

    (Zhejiang University School of Medicine)

  • Yulan Yang

    (Zhejiang University)

  • Chunyan Ruan

    (Zhejiang University)

  • Yi Luo

    (Zhejiang University)

  • Lizhi Song

    (Zhejiang University)

  • Ting Wu

    (Zhejiang University)

  • Jun Huang

    (Zhejiang University School of Medicine
    Zhejiang University)

  • Bing Yang

    (Zhejiang University)

  • Ting Liu

    (Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

Abstract

Replication fork reversal, a critical protective mechanism against replication stress in higher eukaryotic cells, is orchestrated via a series of coordinated enzymatic reactions. The Bloom syndrome gene product, BLM, a member of the highly conserved RecQ helicase family, is implicated in this process, yet its precise regulation and role remain poorly understood. In this study, we demonstrate that the GCFC domain-containing protein TFIP11 forms a complex with the BLM helicase. TFIP11 exhibits a preference for binding to DNA substrates that mimic the structure generated at stalled replication forks. Loss of either TFIP11 or BLM leads to the accumulation of the other protein at stalled forks. This abnormal accumulation, in turn, impairs RAD51-mediated fork reversal and slowing, sensitizes cells to replication stress-inducing agents, and enhances chromosomal instability. These findings reveal a previously unidentified regulatory mechanism that modulates the activities of BLM and RAD51 at stalled forks, thereby impacting genome integrity.

Suggested Citation

  • Junliang Chen & Mingjie Wu & Yulan Yang & Chunyan Ruan & Yi Luo & Lizhi Song & Ting Wu & Jun Huang & Bing Yang & Ting Liu, 2024. "TFIP11 promotes replication fork reversal to preserve genome stability," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45684-3
    DOI: 10.1038/s41467-024-45684-3
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