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

Manickam Gurusaran, Jingjing Zhang, Kexin Zhang, Hiroki Shibuya and Owen R. Davies ()
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Manickam Gurusaran: University of Edinburgh
Jingjing Zhang: University of Gothenburg
Kexin Zhang: University of Gothenburg
Hiroki Shibuya: University of Gothenburg
Owen R. Davies: University of Edinburgh

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-50920-x

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