8PBC

RAD51 filament on ssDNA bound by the BRCA2 c-terminus

8PBC の概要

• エントリーDOI: 10.2210/pdb8pbc/pdb
• EMDBエントリー: 17584
• 分子名称: DNA repair protein RAD51 homolog 1, Breast cancer type 2 susceptibility protein, DNA (30-MER), ... (5 entities in total)
• 機能のキーワード: rad51, brca2, filament, complex, recombination
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 22
• 化学式量合計: 478066.46

構造登録者

Appleby, R.,Pellegrini, L. (登録日: 2023-06-09, 公開日: 2023-11-15)

主引用文献

Appleby, R.,Joudeh, L.,Cobbett, K.,Pellegrini, L.
Structural basis for stabilisation of the RAD51 nucleoprotein filament by BRCA2.
Nat Commun, 14:7003-7003, 2023

PubMed 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.

PubMed: 37919288
DOI: 10.1038/s41467-023-42830-1

実験手法

ELECTRON MICROSCOPY (2.61 Å)