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MEILB2-BRME1 forms a V-shaped DNA clamp upon BRCA2-binding in meiotic recombination
Manickam Gurusaran1, Jingjing Zhang2, Kexin Zhang2
1Wellcome Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh, UK.
Nature Communications
|August 2, 2024
Summary
Meiosis-specific MEILB2-BRME1 protein complex is crucial for DNA repair and crossover formation. BRCA2 binding transforms it into a DNA clamp, bridging DNA ends to facilitate homologous recombination in germ cells.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Homologous recombination repairs DNA double-strand breaks during meiosis.
- This process is essential for generating haploid germ cells.
- Meiosis-specific MEILB2-BRME1 protein complex facilitates recombinase loading onto DNA.
Purpose of the Study:
- To determine the crystal structure of the MEILB2-BRME1 2:2 core complex.
- To elucidate the mechanism by which MEILB2-BRME1 functions in meiotic recombination.
- To understand the role of BRCA2 in regulating MEILB2-BRME1 activity.
Main Methods:
- X-ray crystallography to determine the structure of the MEILB2-BRME1 2:2 core complex.
- In vivo recruitment assays to study BRME1 localization.
- Biochemical assays to investigate complex formation and DNA binding.
Main Results:
- The crystal structure reveals a parallel four-helical assembly of MEILB2-BRME1.
- MEILB2-BRME1 forms an N-terminal β-cap for DNA binding and a coiled-coil region.
- BRCA2 binding induces dimerization into a V-shaped 2:4:4 complex, enabling DNA bridging.
Conclusions:
- MEILB2-BRME1 acts as a DNA clamp, regulated by BRCA2.
- This clamp facilitates the connection of resected DNA ends or homologous chromosomes.
- The mechanism is critical for efficient meiotic recombination and germ cell formation.
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