| 2023 |
FIRRM interacts with and stabilizes the AAA+ ATPase FIGNL1; inactivation of either FIRRM or FIGNL1 results in ultrafine DNA bridge (UFB) formation, prolonged accumulation of RAD51 at nuclear foci, and impaired replication fork dynamics, indicating that FIRRM-FIGNL1 regulates RAD51 dynamics at replication forks to maintain genome integrity. |
Genome-wide loss-of-function screen, co-immunoprecipitation, RAD51 foci analysis, replication fork dynamics assay, UFB imaging |
Cell reports |
High |
37347663
|
| 2021 |
Apolo1 (FIRRM) localizes to kinetochores during early mitosis, sustains PLK1 kinase activity at kinetochores during prometaphase for accurate kinetochore-microtubule attachment, is a cognate substrate of PLK1 (phosphorylated by PLK1), and phosphorylation enables PP1γ to subsequently inactivate PLK1 by dephosphorylation — constituting a feedback loop that governs PLK1 activity. |
FRET-based PLK1 activity reporter, live-cell imaging (kinetochore localization), kinase substrate assay, phosphatase (PP1γ) interaction/dephosphorylation assay, siRNA knockdown with chromosome alignment phenotype |
Cell reports |
High |
34260926
|
| 2023 |
FIRRM is recruited to ICL (interstrand crosslink) sites, controls MUS81 chromatin loading, and thereby mediates resolution of homologous recombination intermediates generated during ICL repair; FIRRM deficiency causes hypersensitivity to ICL agents, DNA damage accumulation in S-G2, chromosomal aberrations, and a unique mutational signature associated with HR deficiency. |
Complementary CRISPR genetic screens, ICL sensitivity assays, cell cycle analysis (DNA damage accumulation in S-G2), chromatin fractionation (MUS81 loading), recruitment to ICLs (laser-induced damage foci), chromosomal aberration analysis, mouse knockout (early embryonic lethality) |
Science advances |
High |
37256941
|
| 2024 |
FIRRM (FLIP/C1orf112) forms a stable complex with FIGNL1 that is required to limit RAD51 amounts and foci on chromatin both in the presence and absence of exogenous DNA damage, and to promote RAD51 dissociation from nucleofilaments to complete HR; FLIP loss causes defective replication fork progression and reduced HR competency. |
Co-immunoprecipitation (stable complex), RAD51 chromatin fractionation/foci quantification, replication fork progression assay (fiber assay), HR reporter assay, ICL sensitivity assay, epistasis analysis |
Nature communications |
High |
38286805
|
| 2024 |
The FIGNL1-FIRRM complex is essential for meiotic recombination; both proteins are required for completing meiotic prophase in mouse spermatocytes, and the complex limits RAD51 and DMC1 accumulation on intact chromatin independently of SPO11-catalyzed DSBs. Purified human FIGNL1ΔN alters the RAD51/DMC1 nucleoprotein filament structure and inhibits strand invasion in vitro. |
Male germline-specific conditional knockout (cKO) mouse models, immunofluorescence (RAD51/DMC1 foci), in vitro strand invasion assay with purified proteins, nucleoprotein filament structure analysis |
Nature communications |
High |
39147779
|
| 2023 |
FIRRM cooperates with FIGNL1 to promote resolution of RAD51 foci at ICL-induced DSBs; FIRRM stability is interdependent with FIGNL1. A FIRRM mutant lacking the WCF domain (ΔWCF) stabilizes FIRRM independently of FIGNL1 and rescues RAD51 foci resolution and cell survival, suggesting FIGNL1-independent function. FIRRM also binds preferentially to single-stranded DNA in vitro. |
CRISPR screen, Co-immunoprecipitation (FIRRM-FIGNL1 complex/stability), RAD51 foci analysis, domain-deletion mutagenesis (ΔWCF), in vitro ssDNA binding assay |
Science advances |
High |
37556550
|
| 2023 |
C1orf112 (FIRRM) physically interacts with FIGNL1, enhances FIGNL1 protein stability, and directly stimulates the RAD51 filament disassembly activity of FIGNL1. BRCA2 directly interacts with the C1orf112-FIGNL1 complex and functions upstream to protect RAD51 filaments from premature disassembly by this complex. |
RAD51 proximity proteomics, Co-immunoprecipitation, in vitro RAD51 filament disassembly assay with purified proteins, protein stability assay, epistasis analysis (BRCA2 upstream) |
Cell reports |
High |
37515771
|
| 2023 |
The in vitro reconstitution of RAD51 filament disassembly by purified C1orf112/FIRRM-FIGNL1 complex was validated, and the antagonistic effect between C1orf112/FIRRM-FIGNL1 and BRCA2 on RAD51 filament stabilization was demonstrated biochemically using purified proteins from E. coli or S. cerevisiae. |
Protein purification from E. coli and S. cerevisiae, in vitro RAD51 filament disassembly reconstitution, competition assay with purified miBRCA2 |
STAR protocols |
High |
38133958
|
| 2026 |
FIRRM knockout in hepatocellular carcinoma cells reduces PLK1 phosphorylation and inhibits mitotic progression and the G2-to-M transition of the cell cycle, establishing that FIRRM promotes mitotic entry via PLK1-mediated signaling. |
CRISPR knockout of FIRRM in HCC cell lines, PLK1 phosphorylation assay (western blot), cell cycle analysis (flow cytometry), in vivo tumor proliferation assay |
Journal of gastroenterology |
Medium |
42007975
|
| 2024 |
Methionine restriction reduces C1orf112 expression in osteosarcoma cells, and reduced C1orf112 expression underlies methionine deprivation-initiated suppression of mitochondrial functions (dysregulated respiratory chain gene expression, increased mitochondrial ROS, reduced ATP production, decreased respiration, damaged mitochondrial membrane potential). |
Transcriptomic analysis, C1orf112 expression knockdown in cultured cells, mitochondrial function assays (ROS, ATP, oxygen consumption, membrane potential), xenograft models |
Cell death & disease |
Medium |
38769167
|