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SART3 promotes homologous recombination repair by stimulating DNA-RNA hybrids removal and DNA end resection

Author

Listed:
  • Hui Fu

    (China National Center for Bioinformation
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Min Huang

    (Chinese Academy of Sciences)

  • Honglin Wu

    (University of Chinese Academy of Sciences
    Chinese Academy of Sciences
    Beijing Institute for Stem Cell and Regenerative Medicine)

  • Hui Zheng

    (China National Center for Bioinformation
    Chinese Academy of Sciences)

  • Yifei Gong

    (China National Center for Bioinformation
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Lingyu Xing

    (Chinese Academy of Sciences)

  • Juanjuan Gong

    (Chinese Academy of Sciences)

  • Ruiyuan An

    (China National Center for Bioinformation
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Qian Li

    (China National Center for Bioinformation
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Xinyu Jie

    (University of Chinese Academy of Sciences
    Chinese Academy of Sciences
    Beijing Institute for Stem Cell and Regenerative Medicine)

  • Xiaolu Ma

    (Chinese Academy of Sciences
    Taiyuan University of Technology)

  • Tie-Shan Tang

    (University of Chinese Academy of Sciences
    Chinese Academy of Sciences
    Beijing Institute for Stem Cell and Regenerative Medicine)

  • Caixia Guo

    (China National Center for Bioinformation
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

Abstract

DNA–RNA hybrids triggered by double-strand breaks (DSBs) are crucial intermediates during DSB repair, and their timely resolution requires numbers of RNA helicases, including DEAD box 1 (DDX1). However, how these helicases are recruited to DSB-induced hybrids in time remains largely unclear. Here, we revealed that squamous cell carcinoma antigen recognized by T cells 3 (SART3) promotes DDX1 binding to DNA–RNA hybrids at DSBs for optimal homologous recombination (HR) repair. SART3 itself associates with DNA–RNA hybrids and PAR chains and accumulates at DSBs in both PARylation- and DNA–RNA hybrids-dependent fashion. SART3 also associates with DDX1 and is necessary for DDX1 enrichment at DSBs. The defective SART3-DDX1 association observed in cells expressing the cancer-associated variant SART3-R836W impairs not only the accumulation of DDX1, but also hybrid removal and HR efficiency. Moreover, SART3 promotes DNA end resection through enhancing USP15-BARD1 association and BRCA1-BARD1 retention. Together, our study reveals an role of SART3 in DSB repair, rendering SART3 a promising target for cancer therapy.

Suggested Citation

  • Hui Fu & Min Huang & Honglin Wu & Hui Zheng & Yifei Gong & Lingyu Xing & Juanjuan Gong & Ruiyuan An & Qian Li & Xinyu Jie & Xiaolu Ma & Tie-Shan Tang & Caixia Guo, 2025. "SART3 promotes homologous recombination repair by stimulating DNA-RNA hybrids removal and DNA end resection," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57599-8
    DOI: 10.1038/s41467-025-57599-8
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    References listed on IDEAS

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    1. Eleni P. Mimitou & Lorraine S. Symington, 2008. "Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing," Nature, Nature, vol. 455(7214), pages 770-774, October.
    2. Magdalena P. Crossley & Chenlin Song & Michael J. Bocek & Jun-Hyuk Choi & Joseph N. Kousouros & Ataya Sathirachinda & Cindy Lin & Joshua R. Brickner & Gongshi Bai & Hannes Lans & Wim Vermeulen & Month, 2023. "R-loop-derived cytoplasmic RNA–DNA hybrids activate an immune response," Nature, Nature, vol. 613(7942), pages 187-194, January.
    3. Hengyao Niu & Woo-Hyun Chung & Zhu Zhu & Youngho Kwon & Weixing Zhao & Peter Chi & Rohit Prakash & Changhyun Seong & Dongqing Liu & Lucy Lu & Grzegorz Ira & Patrick Sung, 2010. "Mechanism of the ATP-dependent DNA end-resection machinery from Saccharomyces cerevisiae," Nature, Nature, vol. 467(7311), pages 108-111, September.
    4. Sarah Cohen & Nadine Puget & Yea-Lih Lin & Thomas Clouaire & Marion Aguirrebengoa & Vincent Rocher & Philippe Pasero & Yvan Canitrot & Gaëlle Legube, 2018. "Senataxin resolves RNA:DNA hybrids forming at DNA double-strand breaks to prevent translocations," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    5. Elda Cannavo & Petr Cejka, 2014. "Sae2 promotes dsDNA endonuclease activity within Mre11–Rad50–Xrs2 to resect DNA breaks," Nature, Nature, vol. 514(7520), pages 122-125, October.
    6. Christine Richardson & Maria Jasin, 2000. "Frequent chromosomal translocations induced by DNA double-strand breaks," Nature, Nature, vol. 405(6787), pages 697-700, June.
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