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A meiosis-specific BRCA2 binding protein recruits recombinases to DNA double-strand breaks to ensure homologous recombination

Author

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  • Jingjing Zhang

    (University of Gothenburg)

  • Yasuhiro Fujiwara

    (University of Tokyo)

  • Shohei Yamamoto

    (University of Tokyo)

  • Hiroki Shibuya

    (University of Gothenburg)

Abstract

Homologous recombination (HR) repairs DNA double-strand breaks (DSBs) to maintain genomic integrity. Recombinase recruited to the DSBs by the mediator protein BRCA2 catalyzes the homology-directed repair. During meiotic HR, programmed DSBs are introduced genome-wide but their repair mechanisms, including the regulation of BRCA2, have remained largely elusive. Here we identify a meiotic localizer of BRCA2, MEILB2/HSF2BP, that localizes to the site of meiotic DSBs in mice. Disruption of Meilb2 abolishes the localization of RAD51 and DMC1 recombinases in spermatocytes, leading to errors in DSB repair and male sterility. MEILB2 directly binds to BRCA2 and regulates its association to meiotic DSBs. We map the MEILB2-binding domain within BRCA2 that is distinct from the canonical DNA-binding domain but is sufficient to localize to meiotic DSBs in a MEILB2-dependent manner. We conclude that localization of BRCA2 to meiotic DSBs is mediated by MEILB2, which is an integral mechanism to repair abundant meiotic DSBs.

Suggested Citation

  • Jingjing Zhang & Yasuhiro Fujiwara & Shohei Yamamoto & Hiroki Shibuya, 2019. "A meiosis-specific BRCA2 binding protein recruits recombinases to DNA double-strand breaks to ensure homologous recombination," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08676-2
    DOI: 10.1038/s41467-019-08676-2
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    Cited by:

    1. Jingjing Zhang & Mario Ruiz & Per-Olof Bergh & Marcus Henricsson & Nena Stojanović & Ranjan Devkota & Marius Henn & Mohammad Bohlooly-Y & Abrahan Hernández-Hernández & Manfred Alsheimer & Jan Borén &, 2024. "Regulation of meiotic telomere dynamics through membrane fluidity promoted by AdipoR2-ELOVL2," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. James M. Dunce & Owen R. Davies, 2024. "BRCA2 stabilises RAD51 and DMC1 nucleoprotein filaments through a conserved interaction mode," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    3. Manickam Gurusaran & Jingjing Zhang & Kexin Zhang & Hiroki Shibuya & Owen R. Davies, 2024. "MEILB2-BRME1 forms a V-shaped DNA clamp upon BRCA2-binding in meiotic recombination," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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