Structural basis for stabilisation of the RAD51 nucleoprotein filament by BRCA2

Robert Appleby, Luay Joudeh, Katie Cobbett and Luca Pellegrini ()
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Robert Appleby: University of Cambridge
Luay Joudeh: University of Cambridge
Katie Cobbett: University of Cambridge
Luca Pellegrini: University of Cambridge

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: 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.

Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42830-1

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DOI: 10.1038/s41467-023-42830-1

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