Molecular basis of FIGNL1 in dissociating RAD51 from DNA and chromatin Journal Article
| Authors: | Carver, A.; Yu, T. Y.; Yates, L. A.; White, T.; Wang, R.; Lister, K.; Jasin, M.; Zhang, X. D. |
| Article Title: | Molecular basis of FIGNL1 in dissociating RAD51 from DNA and chromatin |
| 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. |
| Keywords: | homologous recombination; protein; overexpression; disruption; complexes; insights; dmc1; filaments; beam-induced motion |
| Journal Title: | Science |
| Volume: | 387 |
| Issue: | 6732 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2025-01-24 |
| Start Page: | 426 |
| End Page: | 431 |
| Language: | English |
| ACCESSION: | WOS:001496574700034 |
| DOI: | 10.1126/science.adr7920 |
| PROVIDER: | wos |
| PMCID: | PMC7617353 |
| PUBMED: | 39636933 |
| Notes: | Source: Wos |
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