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MEILB2-BRME1 forms a V-shaped DNA clamp upon BRCA2-binding in meiotic recombination

Author

Listed:
  • Manickam Gurusaran

    (University of Edinburgh)

  • Jingjing Zhang

    (University of Gothenburg)

  • Kexin Zhang

    (University of Gothenburg)

  • Hiroki Shibuya

    (University of Gothenburg
    RIKEN Center for Biosystems Dynamics Research (BDR))

  • Owen R. Davies

    (University of Edinburgh)

Abstract

DNA double-strand break repair by homologous recombination has a specialised role in meiosis by generating crossovers that enable the formation of haploid germ cells. This requires meiosis-specific MEILB2-BRME1, which interacts with BRCA2 to facilitate loading of recombinases onto resected DNA ends. Here, we report the crystal structure of the MEILB2-BRME1 2:2 core complex, revealing a parallel four-helical assembly that recruits BRME1 to meiotic double-strand breaks in vivo. It forms an N-terminal β-cap that binds to DNA, and a MEILB2 coiled-coil that bridges to C-terminal ARM domains. Upon BRCA2-binding, MEILB2-BRME1 2:2 complexes dimerize into a V-shaped 2:4:4 complex, with rod-like MEILB2-BRME1 components arranged at right-angles. The β-caps located at the tips of the MEILB2-BRME1 limbs are separated by 25 nm, allowing them to bridge between DNA molecules. Thus, we propose that BRCA2 induces MEILB2-BRME1 to function as a DNA clamp, connecting resected DNA ends or homologous chromosomes to facilitate meiotic recombination.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50920-x
    DOI: 10.1038/s41467-024-50920-x
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