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Bre1/RNF20 promotes Rad51-mediated strand exchange and antagonizes the Srs2/FBH1 helicases

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  • Guangxue Liu

    (Renmin Hospital of Wuhan University, Wuhan University)

  • Jimin Li

    (Renmin Hospital of Wuhan University, Wuhan University)

  • Boxue He

    (University of Texas Health Science Center)

  • Jiaqi Yan

    (Renmin Hospital of Wuhan University, Wuhan University)

  • Jingyu Zhao

    (Renmin Hospital of Wuhan University, Wuhan University)

  • Xuejie Wang

    (Renmin Hospital of Wuhan University, Wuhan University)

  • Xiaocong Zhao

    (Wuhan University)

  • Jingyan Xu

    (Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School)

  • Yeyao Wu

    (Zhejiang University School of Medicine)

  • Simin Zhang

    (Renmin Hospital of Wuhan University, Wuhan University)

  • Xiaoli Gan

    (Renmin Hospital of Wuhan University, Wuhan University)

  • Chun Zhou

    (Zhejiang University School of Medicine)

  • Xiangpan Li

    (Renmin Hospital of Wuhan University, Wuhan University)

  • Xinghua Zhang

    (Renmin Hospital of Wuhan University, Wuhan University
    Wuhan University)

  • Xuefeng Chen

    (Renmin Hospital of Wuhan University, Wuhan University)

Abstract

Central to homologous recombination (HR) is the assembly of Rad51 recombinase on single-strand DNA (ssDNA), forming the Rad51-ssDNA filament. How the Rad51 filament is efficiently established and sustained remains partially understood. Here, we find that the yeast ubiquitin ligase Bre1 and its human homolog RNF20, a tumor suppressor, function as recombination mediators, promoting Rad51 filament formation and subsequent reactions via multiple mechanisms independent of their ligase activities. We show that Bre1/RNF20 interacts with Rad51, directs Rad51 to ssDNA, and facilitates Rad51-ssDNA filament assembly and strand exchange in vitro. In parallel, Bre1/RNF20 interacts with the Srs2 or FBH1 helicase to counteract their disrupting effect on the Rad51 filament. We demonstrate that the above functions of Bre1/RNF20 contribute to HR repair in cells in a manner additive to the mediator protein Rad52 in yeast or BRCA2 in human. Thus, Bre1/RNF20 provides an additional layer of mechanism to directly control Rad51 filament dynamics.

Suggested Citation

  • Guangxue Liu & Jimin Li & Boxue He & Jiaqi Yan & Jingyu Zhao & Xuejie Wang & Xiaocong Zhao & Jingyan Xu & Yeyao Wu & Simin Zhang & Xiaoli Gan & Chun Zhou & Xiangpan Li & Xinghua Zhang & Xuefeng Chen, 2023. "Bre1/RNF20 promotes Rad51-mediated strand exchange and antagonizes the Srs2/FBH1 helicases," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38617-z
    DOI: 10.1038/s41467-023-38617-z
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