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TitleStructural basis for stabilisation of the RAD51 nucleoprotein filament by BRCA2.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 7003, Year 2023
Publish dateNov 2, 2023
AuthorsRobert Appleby / Luay Joudeh / Katie Cobbett / Luca Pellegrini /
PubMed AbstractThe 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- ...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.
External linksNat Commun / PubMed:37919288 / PubMed Central
MethodsEM (helical sym.)
Resolution2.61 - 2.83 Å
Structure data

17584

8pbc

EMDB-17584, PDB-8pbc:
RAD51 filament on ssDNA bound by the BRCA2 c-terminus
Method: EM (helical sym.) / Resolution: 2.61 Å

17585

8pbd

EMDB-17585, PDB-8pbd:
RAD51 filament on dsDNA bound by the BRCA2 c-terminus
Method: EM (helical sym.) / Resolution: 2.83 Å

Chemicals

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-CA:
Unknown entry

Source
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsRECOMBINATION / RAD51 / BRCA2 / Filament / Complex

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