6R3P

Crystal structure of human DMC1 ATPase domain

Summary for 6R3P

• Entry DOI: 10.2210/pdb6r3p/pdb
• Descriptor: Meiotic recombination protein DMC1/LIM15 homolog, 1,2-ETHANEDIOL, DI(HYDROXYETHYL)ETHER, ... (7 entities in total)
• Functional Keywords: recombinase, homologous recombination, strand invasion, meiosis, recombination
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 116808.79

Authors

Dunce, J.M.,Davies, O.R. (deposition date: 2019-03-20, release date: 2019-04-03, Last modification date: 2024-12-04)

Primary citation

Dunce, J.M.,Davies, O.R.
BRCA2 stabilises RAD51 and DMC1 nucleoprotein filaments through a conserved interaction mode.
Nat Commun, 15:8292-8292, 2024

PubMed Abstract: BRCA2 is essential for DNA repair by homologous recombination in mitosis and meiosis. It interacts with recombinases RAD51 and DMC1 to facilitate the formation of nucleoprotein filaments on resected DNA ends that catalyse recombination-mediated repair. BRCA2's BRC repeats bind and disrupt RAD51 and DMC1 filaments, whereas its PhePP motifs bind recombinases and stabilise their nucleoprotein filaments. However, the mechanism of filament stabilisation has hitherto remained unknown. Here, we report the crystal structure of a BRCA2-DMC1 complex, revealing how core interaction sites of PhePP motifs bind to recombinases. The interaction mode is conserved for RAD51 and DMC1, which selectively bind to BRCA2's two distinct PhePP motifs via subtly divergent binding pockets. PhePP motif sequences surrounding their core interaction sites protect nucleoprotein filaments from BRC-mediated disruption. Hence, we report the structural basis of how BRCA2's PhePP motifs stabilise RAD51 and DMC1 nucleoprotein filaments for their essential roles in mitotic and meiotic recombination.

PubMed: 39333100
DOI: 10.1038/s41467-024-52699-3

Experimental method

X-RAY DIFFRACTION (2.05 Å)