Summary information and primary citation
- PDB-id
- 8pbc; DSSR-derived features in text and JSON formats
- Class
- recombination
- Method
- cryo-EM (2.61 Å)
- Summary
- Rad51 filament on ssDNA bound by the brca2 c-terminus
- Reference
- Appleby R, Joudeh L, Cobbett K, Pellegrini L (2023): "Structural basis for stabilisation of the RAD51 nucleoprotein filament by BRCA2." Nat Commun, 14, 7003. doi: 10.1038/s41467-023-42830-1.
- Abstract
- The BRCA2 tumour suppressor protein preserves genomic integrity via interactions with the DNA-strand exchange RAD51 protein in homology-directed repair. The RAD51-binding TR2 motif at the BRCA2 C-terminus is essential for protection and restart of stalled replication forks. Biochemical evidence shows that TR2 recognises filamentous RAD51, but existing models of TR2 binding to RAD51 lack a structural basis. Here we used cryo-electron microscopy and structure-guided mutagenesis to elucidate the mechanism of TR2 binding to nucleoprotein filaments of human RAD51. We find that TR2 binds across the protomer interface in the filament, acting as a brace for adjacent RAD51 molecules. TR2 targets an acidic-patch motif on human RAD51 that serves as a recruitment hub in fission yeast Rad51 for recombination mediators Rad52 and Rad55-Rad57. Our findings provide a structural rationale for RAD51 filament stabilisation by BRCA2 and reveal a common recruitment mechanism of recombination mediators to the RAD51 filament.
