8R64

Cryo-EM structure of the FIGNL1 AAA hexamer bound to RAD51

Summary for 8R64

• Entry DOI: 10.2210/pdb8r64/pdb
• EMDB information: 18946
• Descriptor: Fidgetin-like protein 1, DNA repair protein RAD51 homolog 1, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: aaa, atpase, dna repair, hydrolase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 7
• Total formula weight: 317045.09

Authors

Carver, A.,Yates, L.A.,Zhang, X. (deposition date: 2023-11-20, release date: 2024-09-04, Last modification date: 2025-07-02)

Primary citation

Carver, A.,Yu, T.Y.,Yates, L.A.,White, T.,Wang, R.,Lister, K.,Jasin, M.,Zhang, X.
Molecular basis of FIGNL1 in dissociating RAD51 from DNA and chromatin.
Science, 387:426-431, 2025

PubMed Abstract: Maintaining genome integrity is an essential and challenging process. RAD51 recombinase, the central component of several crucial processes in repairing DNA and protecting genome integrity, forms filaments on DNA, which are tightly regulated. One of these RAD51 regulators is FIGNL1 (fidgetin-like 1), which prevents RAD51 genotoxic chromatin association in normal cells and persistent RAD51 foci upon DNA damage. The cryogenic electron microscopy-imaged structure of FIGNL1 in complex with RAD51 reveals that FIGNL1 forms a nonplanar hexamer and encloses RAD51 N terminus in the FIGNL1 hexamer pore. Mutations in pore loop or catalytic residues of FIGNL1 render it defective in filament disassembly and are lethal in mouse embryonic stem cells. Our study reveals a distinct mechanism for removing RAD51 from bound substrates and provides the molecular basis for FIGNL1 in maintaining genome stability.

PubMed: 39636933
DOI: 10.1126/science.adr7920

Experimental method

ELECTRON MICROSCOPY (3.2 Å)