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-Structure paper
タイトル | Structural basis for stabilisation of the RAD51 nucleoprotein filament by BRCA2. |
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ジャーナル・号・ページ | Nat Commun, Vol. 14, Issue 1, Page 7003, Year 2023 |
掲載日 | 2023年11月2日 |
著者 | Robert Appleby / Luay Joudeh / Katie Cobbett / Luca Pellegrini / |
PubMed 要旨 | 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- ...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. |
リンク | Nat Commun / PubMed:37919288 / PubMed Central |
手法 | EM (らせん対称) |
解像度 | 2.61 - 2.83 Å |
構造データ | EMDB-17584, PDB-8pbc: EMDB-17585, PDB-8pbd: |
化合物 | ChemComp-ATP: ChemComp-CA: |
由来 |
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キーワード | RECOMBINATION / RAD51 / BRCA2 / Filament / Complex |