Structural basis for stabilisation of the RAD51 nucleoprotein filament by BRCA2.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 11 2023
02 11 2023
Historique:
received:
18
07
2023
accepted:
23
10
2023
medline:
6
11
2023
pubmed:
3
11
2023
entrez:
3
11
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37919288
doi: 10.1038/s41467-023-42830-1
pii: 10.1038/s41467-023-42830-1
pmc: PMC10622577
doi:
Substances chimiques
DNA-Binding Proteins
0
Nucleoproteins
0
Rad51 Recombinase
EC 2.7.7.-
BRCA2 Protein
0
RAD51 protein, human
EC 2.7.7.-
BRCA2 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7003Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
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