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PreprintCited by 25DNA Repair MechanismsDNA and Nucleic Acid ChemistryProtein Structure and Dynamics

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Molecular basis of FIGNL1 in dissociating RAD51 from DNA and chromatin

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Carver, Alexander, Yu, Tai-Yuan, Yates, Luke A, White, Travis, Wang, Raymond, Lister, Katie, Jasin, Maria, Zhang, Xiaodong·2024·Science
DOI 10.1101/2024.07.16.603765PMC PMC7617353

Preprint — published as 10.1126/science.adr7920 · Paper page

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Abstract

Maintaining genome integrity is an essential and challenging process. RAD51 recombinase, the central player of several crucial processes in repairing and protecting genome integrity, forms filaments on DNA. RAD51 filaments are tightly regulated. One of these regulators is FIGNL1, that prevents persistent RAD51 foci post-damage and genotoxic chromatin association in cells. The cryogenic electron microscopy structure of FIGNL1 in complex with RAD51 reveals that the FIGNL1 forms a non-planar hexamer and RAD51 N-terminus is enclosed 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 unique mechanism for removing RAD51 from DNA and provides the molecular basis for FIGNL1 in maintaining genome stability.

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Metadata

Authors
Carver, A., Yu, T.-Y., Yates, L. A., White, T., Wang, R., Lister, K., Jasin, M., & Zhang, X.
Affiliations
  • The Francis Crick Institute (GB)
  • Memorial Sloan Kettering Cancer Center (US)
Corresponding author
  • Jasin, Maria
  • Zhang, Xiaodong
ORCID
Venue
Science
Publisher
openRxiv
Published
2024-07-16
Volume
387
Issue
6732
Pages
426-431
ISSN
0036-8075 (ISSN-L)
DOI
10.1101/2024.07.16.603765
PMC
PMC7617353
OpenAlex
W4405056751
Cited by
25
References
1
Citations by year
2026: 8 · 2025: 15 · 2024: 2
FWCI
3.40
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Science (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
  • Figshare (submittedVersion, cc-by)
  • The Francis Crick Institute (cc-by)
Funders
  • Wellcome Trust (227769/Z/23/Z, CC0103, 210658/Z/18/Z, 098412/Z/12/Z, 227769)
  • Diamond Light Source
  • Cancer Research UK (CC0103)
  • Imperial College London
  • National Institutes of Health
  • Medical Research Council (MR/Y001192/1)
  • National Cancer Institute (P30CA008748, R35CA253174)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
FIGNL1, RAD51, genome stability, DNA repair, protein complex structure, mouse embryonic stem cells

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