| 2013 |
FIGNL1 specifically interacts with RAD51 through a conserved RAD51-binding domain. FIGNL1 is recruited to sites of DNA damage independently of BRCA2, RAD51, and RAD51 paralogs. FIGNL1 depletion causes defective HR repair but does not affect RAD51 loading onto ssDNA. FIGNL1 forms a complex with KIAA0146/SPIDR, which acts together with FIGNL1 in HR repair. |
Co-immunoprecipitation, domain mapping, siRNA knockdown, HR reporter assay, immunofluorescence foci analysis |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
23754376
|
| 2019 |
Purified FIGNL1 promotes dissociation of RAD51 from ssDNA in vitro (anti-recombinase activity). This RAD51-dismantling activity does not require FIGNL1 ATPase activity but depends on RAD51-binding. The RAD51 paralogue SWSAP1 binds both RAD51 and FIGNL1, and purified SWSAP1 inhibits the RAD51-dismantling activity of FIGNL1, thereby protecting RAD51 filaments. Depletion of FIGNL1 suppresses the defective RAD51 assembly seen in SWSAP1-depleted cells (genetic epistasis). |
In vitro RAD51-ssDNA dissociation assay with purified proteins, ATPase-dead mutagenesis, siRNA epistasis, RAD51 foci immunofluorescence |
Nature communications |
High |
30926776
|
| 2023 |
C1orf112/FLIP forms a stable complex with FIGNL1. Loss of FLIP leads to increased RAD51 amounts and foci on chromatin (with or without DNA damage), defective replication fork progression, and reduced HR competency, consistent with FLIP being required for RAD51 dissociation from nucleofilaments. Both proteins have epistatic roles in ICL repair. |
Co-immunoprecipitation, siRNA/CRISPR KO, RAD51 chromatin fractionation, replication fork assay, HR reporter assay |
bioRxivpreprint |
Medium |
37808755
|
| 2023 |
C1orf112/FIRRM physically interacts with FIGNL1 and enhances FIGNL1 protein stability. The RAD51 filament disassembly activity of FIGNL1 is directly stimulated by C1orf112 in vitro. BRCA2 directly interacts with the C1orf112-FIGNL1 complex and functions upstream to protect RAD51 filament from premature disassembly. C1orf112- and FIGNL1-deficient cells are primarily sensitive to DNA ICL agents. |
RAD51 proximity proteomics, Co-IP, in vitro RAD51 filament disassembly assay with purified proteins, CRISPR KO, DNA damage sensitivity assays |
Cell reports |
High |
37515771
|
| 2023 |
The FLIP-FIGNL1 complex regulates RAD51 and DMC1 dissociation to promote meiotic recombination and replication fork restart. FLIP interacts with FIGNL1; depletion of either protein destabilizes the other and impairs RAD51 dissociation. FLIP-null meiocytes accumulate massive RAD51 and DMC1 foci, arrested at a zygotene-like stage. |
Co-immunoprecipitation, germline-specific conditional knockout mice, RAD51/DMC1 immunofluorescence on meiotic spreads, replication fork restart assay |
Nucleic acids research |
High |
37439366
|
| 2023 |
FIRRM (FIGNL1 Interacting Regulator of Recombination and Mitosis) was identified as a FIGNL1 partner required for RAD51 foci resolution at ICL-induced DSBs. FIGNL1 and FIRRM stability is interdependent. FIRRM binds preferentially to single-stranded DNA in vitro. A FIRRM mutant (ΔWCF) that is stable without FIGNL1 can rescue RAD51 foci resolution and cell survival, indicating FIRRM has FIGNL1-independent function in DNA repair. |
CRISPR screen, Co-IP, RAD51 foci immunofluorescence, in vitro ssDNA binding assay, domain mutagenesis, cell survival assay |
Science advances |
Medium |
37556550
|
| 2023 |
FIGNL1 germline-specific conditional knockout male mice show defective chromosome synapsis, impaired meiotic DSB repair, and accumulation of RAD51/DMC1 on meiotic chromosomes. FIGNL1-cKO spermatocytes also accumulate RAD51/DMC1 in pre-meiotic S-phase independently of SPO11-generated DSBs. Purified FIGNL1 dismantles RAD51 filaments on double-stranded DNA as well as ssDNA, indicating a role in limiting non-productive RAD51/DMC1 assembly on native dsDNA. |
Germline-specific conditional knockout mouse, meiotic chromosome spread immunofluorescence, in vitro RAD51 filament disassembly assay with purified protein on dsDNA and ssDNA |
Nature communications |
High |
37891173
|
| 2024 |
Cryo-EM structure of FIGNL1 in complex with RAD51 reveals that FIGNL1 forms a non-planar hexamer that encloses the RAD51 N-terminus within its hexamer pore. Mutations in FIGNL1 pore loop or catalytic (ATPase) residues abolish filament disassembly activity and are lethal in mouse embryonic stem cells, establishing that ATPase activity and pore loop engagement with RAD51 N-terminus are mechanistically essential for RAD51 removal. |
Cryo-EM structure determination, active-site mutagenesis (pore loop and ATPase mutants), in vitro RAD51 filament disassembly assay, mouse embryonic stem cell lethality assay |
Science (New York, N.Y.) |
High |
39636933
|
| 2024 |
FIGNL1 knockout human cells accumulate ultra-fine chromosome bridges (UFBs) between sister chromatids at telomeres and centromeres after replication stress. These UFBs depend on RAD51 (not replication fork stalling per se), and are suppressed by FIGNL1, indicating that FIGNL1-mediated post-replicative RAD51 disassembly prevents recombination intermediate-like UFBs and catastrophic genome instability. FIGNL1 is defective in RAD51 dissociation after replication fork restart in its absence. |
FIGNL1 CRISPR KO human cells, ultra-fine bridge immunofluorescence (FANCD2/BLM markers), RAD51 foci after fork restart, epistasis with RAD51 inhibitor |
Nucleic acids research |
High |
38597669
|
| 2024 |
The FIGNL1-FIRRM complex is required for completing meiotic prophase in mouse spermatocytes. Both proteins limit RAD51 and DMC1 accumulation on intact chromatin independently of SPO11-catalyzed DSB formation. Purified human FIGNL1ΔN alters the RAD51/DMC1 nucleoprotein filament structure and inhibits strand invasion in vitro, placing FIGNL1-FIRRM activity at a post-assembly step to promote strand invasion and processing of recombination intermediates. |
Male germline-specific conditional KO mice, meiotic chromosome spreads, in vitro RAD51/DMC1 filament alteration and strand invasion assay with purified FIGNL1ΔN |
Nature communications |
High |
39147779
|
| 2024 |
FLIP (C1orf112) loss causes increased RAD51 chromatin association, defective replication fork progression, elevated chromosomal instability, and reduced HR competency. FLIP and FIGNL1 form a stable epistatic complex with co-dependent protein stability, and the complex is required for RAD51 dissociation from nucleofilaments upon ICL damage. |
CRISPR KO, RAD51 chromatin fractionation, replication fork progression assay (DNA fiber), HR reporter assay, Co-IP, chromosomal instability/micronuclei quantification |
Nature communications |
High |
38286805
|
| 2024 |
Cryo-EM structure of FIGNL1-RAD51 complex (preprint version): FIGNL1 forms a non-planar hexamer enclosing RAD51 N-terminus in the hexamer pore. Pore loop and ATPase catalytic mutants are defective in RAD51 filament disassembly and lethal in mouse ES cells. |
Cryo-EM structure, mutagenesis, in vitro filament disassembly assay, mouse ES cell lethality |
bioRxivpreprint |
Medium |
39071279
|
| 2025 |
Loss of FIGNL1 (anti-recombinase) restores RAD51 loading at DSBs in BRCA2-deficient cells, leading to genome stability, HR proficiency, and viability of BRCA2-deficient mouse embryonic stem cells. Mechanistically, HR defects upon BRCA2 loss arise primarily from unrestricted FIGNL1-mediated removal of RAD51 from DSBs rather than from defective RAD51 loading. The MMS22L-TONSL complex interacts with FIGNL1 and is critical for HR in BRCA2/FIGNL1 double-deficient cells. |
FIGNL1 KO in BRCA2-deficient mouse ES cells, RAD51 foci at DSBs, HR reporter assay, Co-IP (MMS22L-TONSL-FIGNL1 interaction), viability assay |
Science (New York, N.Y.) |
High |
41166468
|
| 2023 |
In vitro reconstitution protocol established: purified C1orf112/FIRRM-FIGNL1 complex directly disassembles RAD51 filaments, and BRCA2 antagonizes this disassembly to protect RAD51 filament from premature dismantling. |
In vitro reconstitution with purified C1orf112/FIRRM, FIGNL1, mini-BRCA2, and RAD51 from E. coli or S. cerevisiae; RAD51 filament disassembly assay |
STAR protocols |
Medium |
38133958
|
| 2023 |
Compound heterozygous frameshift mutations in FIGNL1 (c.189del and c.1519_1523del) in a human patient cause loss of FIGNL1 nuclear foci formation, fail to increase foci upon DNA damage (phleomycin), and result in increased chromosomal breakage spontaneously and after mitomycin C exposure, establishing FIGNL1 nuclear foci as functionally important for the DDR. |
Whole exome sequencing, transfection of DYK-tagged FIGNL1 mutant constructs in HEK293 cells, nuclear foci quantification, chromosomal breakage assay |
European journal of endocrinology |
Medium |
37740949
|