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

Gurusaran, Manickam (author)
Zhang, Jingjing, 1986 (author)
Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
Zhang, Kexin, 1993 (author)
Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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Shibuya, Hiroki, 1985 (author)
Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
Davies, Owen R. (author)
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 (creator_code:org_t)
2024
2024
English.
In: NATURE COMMUNICATIONS. - 2041-1723. ; 15:1
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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 beta-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 beta-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. MEILB2-BRME1 is a BRCA2-binding complex that is required for meiotic recombination. Here, the authors report the structure and DNA-binding of MEILB2-BRME1, revealing how its BRCA2-induced dimerization forms a V-shaped assembly that may clamp together DNA molecules to facilitate recombination.

Subject headings

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

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