6r3p
Crystal structure of human DMC1 ATPase domainCrystal structure of human DMC1 ATPase domain
Structural highlights
FunctionDMC1_HUMAN May participate in meiotic recombination, specifically in homologous strand assimilation, which is required for the resolution of meiotic double-strand breaks (By similarity). Publication Abstract from PubMedBRCA2 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. BRCA2 stabilises RAD51 and DMC1 nucleoprotein filaments through a conserved interaction mode.,Dunce JM, Davies OR Nat Commun. 2024 Sep 27;15(1):8292. doi: 10.1038/s41467-024-52699-3. PMID:39333100[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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