Affinage

FANCC

Fanconi anemia group C protein · UniProt Q00597

Length
558 aa
Mass
63.4 kDa
Annotated
2026-06-09
100 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FANCC encodes a ~60-kDa protein with dual roles in genome maintenance and cytoprotection, originally defined as a Fanconi anemia gene required for cellular resistance to DNA interstrand cross-linking agents (PMID:8499901, PMID:7517562). As part of a nuclear FA core complex, FANCC assembles with FANCA, FANCG, FANCF, and FANCE in a series of interdependent interactions: FANCA-FANCC binding (PMID:9398857), FANCG-bridged complex formation (PMID:10373536), FANCF incorporation (PMID:11063725), and FANCE-mediated linkage of FANCC to the substrate FANCD2 (PMID:16127171); phosphorylation-dependent nuclear accumulation of this complex defines a common pathway disrupted across multiple FA complementation groups (PMID:9789045). This assembly is required for FANCD2 monoubiquitination, and its loss abrogates that modification, elevates spontaneous chromosomal breakage, and confers selective sensitivity to cross-linking agents (PMID:16762635). Downstream, FANCC promotes homologous recombination and error-prone repair of abasic sites, suppresses sister chromatid exchange, and acts in concert with BLM helicase to maintain genome stability (PMID:15327776, PMID:15616572), operating in parallel pathways with BRCA2 and HELQ (PMID:16687415, PMID:24005041). Independently of the core complex, cytoplasmic FANCC exerts anti-apoptotic functions essential for hematopoietic progenitor survival (PMID:8621788, PMID:8977247): it binds Hsp70 to form a ternary complex that inhibits the pro-apoptotic kinase PKR (PMID:11500375, PMID:12397061), binds non-phosphorylated STAT1 to facilitate its docking and activation at the IFN-gamma receptor (PMID:10848598), and attenuates NADPH cytochrome P450 reductase activity (PMID:9787138). Patient-derived mutant FANCC (L554P) loses both core-complex (FANCA, cdc2) and signaling (STAT1) interactions (PMID:9398857, PMID:9242535, PMID:10848598).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 1993 Medium

    Establishing that FACC encodes a functional ~60-kDa product required for cross-link resistance was the foundational step linking the gene to the FA cellular phenotype.

    Evidence Site-directed mutagenesis (L554P) with MMC complementation assay

    PMID:8499901

    Open questions at the time
    • Single mutation studied
    • No mechanism for how the protein confers resistance
  2. 1994 High

    Determining where the protein resides answered whether FANCC acts at DNA directly or elsewhere — fractionation showed it is predominantly cytoplasmic, unexpected for a DNA-repair gene.

    Evidence Cell fractionation, immunofluorescence, and immunoprecipitation with polyclonal antiserum

    PMID:7517562

    Open questions at the time
    • Identity of co-precipitating FRP-50/FRP-150 not established
    • Functional consequence of cytoplasmic localization unresolved
  3. 1996 High

    Engineered localization constructs tested whether cytoplasmic residence is functionally required, showing cytoplasmic but not nuclear-targeted FANCC corrects the cross-link defect.

    Evidence Targeted NLS/NES fusion constructs with MMC and cross-link induction complementation

    PMID:8621788

    Open questions at the time
    • Apparent tension with later nuclear-complex findings unresolved
    • Cytoplasmic mechanism not yet defined
  4. 1996 Medium

    Hematopoietic survival assays addressed the physiological cellular role, establishing FANCC as an anti-apoptotic, progenitor-survival factor distinct from a proliferation driver.

    Evidence Retroviral gene transfer in factor-deprived 32D/MO7e cells and antisense knockdown in bone marrow progenitor colony assays

    PMID:7518843 PMID:8977247

    Open questions at the time
    • Molecular effectors of anti-apoptosis not yet identified
    • Link to cross-link repair function unclear
  5. 1997 High

    Reciprocal co-IP defined FANCC's first physical partner (FANCA), showing the two form a complex that redistributes to the nucleus and that L554P abolishes binding — connecting genotype to assembly.

    Evidence Co-immunoprecipitation, subcellular fractionation, and cdc2 binding/deletion mapping in synchronized cells

    PMID:9242535 PMID:9398857

    Open questions at the time
    • cdc2 interaction lacks in vitro reconstitution
    • Function of the nuclear FANCA-FANCC complex not yet defined
  6. 1998 Medium

    Studies of cdc2/cyclin B signaling and reciprocal nuclear-accumulation requirements clarified how FANCA and FANCC interdependently localize and connect to cell-cycle checkpoint control after damage.

    Evidence Cyclin B1/phospho-cdc2 western blots in isogenic cells, NLS mutagenesis, fractionation, and complementation

    PMID:9187128 PMID:9742112 PMID:9746759

    Open questions at the time
    • One report failed to detect FAA-FAC interaction, conflicting with others
    • Whether checkpoint signaling is direct or downstream of repair failure unresolved
  7. 1998 Medium

    Surveying complex formation across complementation groups established that FANCA/FANCC binding, phosphorylation, and nuclear accumulation define a single shared FA pathway.

    Evidence Co-IP and fractionation across FA groups A, B, C, E, F, G, H

    PMID:9789045

    Open questions at the time
    • The relevant kinase not identified
    • Mechanistic output of nuclear accumulation undefined
  8. 1998 Medium

    Identifying NADPH cytochrome P450 reductase as a cytoplasmic partner offered a candidate mechanism for FANCC's non-repair, redox-related cytoprotective activity.

    Evidence Co-IP, GST pulldown, FMN competition, and cytochrome c reduction enzymatic assay

    PMID:9787138

    Open questions at the time
    • Physiological relevance to hematopoietic protection not directly shown
    • Single lab, no reconstitution
  9. 1999 High

    Adding FANCG and alpha-spectrin II to the nuclear complex extended the architecture and showed FA proteins stabilize associated nuclear factors.

    Evidence Co-IP, nuclear fractionation, and deletion mapping across FA cell lines

    PMID:10373536 PMID:10551855

    Open questions at the time
    • Functional role of alpha-spectrin II in repair undefined
    • Stoichiometry of the complex unknown
  10. 2000 Medium

    Completing the core complex with FANCF and defining cell-cycle-dependent proteasomal control of FANCC clarified complex composition and how FANCC abundance is regulated.

    Evidence Co-IP/fractionation across FA groups and synchronization with proteasome inhibition and deletion constructs

    PMID:10845936 PMID:11063725

    Open questions at the time
    • E3 ligase targeting FANCC unidentified
    • Functional purpose of cell-cycle-regulated abundance unclear
  11. 2000 High

    Identifying STAT1 binding gave a concrete signaling mechanism for FANCC in cytokine responses, with L554P selectively abolishing it.

    Evidence GST pulldown, co-IP, kinetic binding, and transduction rescue at the IFN-gamma receptor

    PMID:10848598

    Open questions at the time
    • Whether STAT1 docking occurs in the cytoplasm or at the membrane unresolved
    • Connection to repair function absent
  12. 2001 High

    The Hsp70 interaction provided the biochemical basis for FANCC's chaperone-dependent cytoprotection against inflammatory cytokines.

    Evidence GST pulldown, in vitro binding, domain mutagenesis, and IFN-gamma/TNF-alpha cytotoxicity rescue; psoralen cross-linked DNA affinity chromatography

    PMID:11401546 PMID:11500375

    Open questions at the time
    • Direct vs. indirect DNA binding by FANCC not distinguished
    • Downstream anti-apoptotic effector then unidentified
  13. 2002 High

    Showing FANCC-Hsp70 inhibits PKR — reconstituted even in yeast lacking FA orthologs — proved the anti-apoptotic activity is genuinely independent of the FA core complex.

    Evidence In vitro kinase assay, ternary-complex co-IP in mammalian and yeast cells, and survival assay

    PMID:12397061

    Open questions at the time
    • How PKR inhibition integrates with cytokine signaling in vivo unresolved
    • Relative contribution of PKR vs. STAT1 vs. RED branches unquantified
  14. 2002 High

    Placing FANCE between FANCC and the substrate FANCD2 established how the core complex couples to the monoubiquitination output.

    Evidence Retroviral rescue, co-IP, immunofluorescence, and fractionation

    PMID:12239156

    Open questions at the time
    • Catalytic ubiquitination machinery not addressed here
    • Direct FANCC contribution to ubiquitin transfer unclear
  15. 2004 High

    Genetic epistasis in DT40 cells defined FANCC's repair output as promotion of HR plus error-prone abasic-site repair, coordinated with TLS and BLM.

    Evidence Gene disruption, SCE assays, double-mutant epistasis with TLS/HR/BLM mutants, and BLM focus formation

    PMID:15327776 PMID:15616572

    Open questions at the time
    • Biochemical step at which FANCC acts within HR undefined
    • Mechanism of BLM focus dependence unknown
  16. 2004 Medium

    Demonstrating impaired type I IFN/JAK-STAT signaling and reduced Th1 differentiation in FANCC-deficient cells extended the signaling role to immune regulation.

    Evidence Phospho-STAT/JAK/TYK2 western blots and T cell flow cytometry in Fancc-null mice

    PMID:15356134

    Open questions at the time
    • Whether the defect is direct or secondary to apoptosis unresolved
    • Single lab
  17. 2005 High

    Mapping FANCE as the bridge between FANCC and both FANCD2 and FANCF refined the internal wiring of the core complex required for monoubiquitination.

    Evidence Yeast two/three-hybrid, human cell co-IP, random mutagenesis screen, and functional complementation

    PMID:16127171

    Open questions at the time
    • Catalytic mechanism of FANCD2 monoubiquitination not addressed
    • Stoichiometry of the ternary complex undefined
  18. 2006 Medium

    Endogenous gene disruption in human cancer cells and FANCE-localization studies confirmed FANCC controls FANCD2 monoubiquitination and selective cross-linker sensitivity, and that FANCC specifically governs FANCE nuclear accumulation.

    Evidence Targeted disruption with monoubiquitination, drug-sensitivity, and cytogenetic assays; co-IP and NES fusion localization constructs

    PMID:16513431 PMID:16762635

    Open questions at the time
    • Single lab
    • Direct enzymatic role of FANCC in ubiquitination unresolved
  19. 2006 Medium

    Epistasis with BRCA2 distinguished FANCC's cross-link pathway from BRCA2/Rad51-mediated repair, showing they act in parallel for ICL repair despite convergence for X-ray damage.

    Evidence DT40 double-mutant survival, chromosomal aberration analysis, and Rad51/FancD2 focus assays

    PMID:16687415

    Open questions at the time
    • Molecular point of pathway divergence undefined
    • Single lab
  20. 2009 Medium

    Mouse genetics revealed a telomere-specific genome-protective role, with FANCC suppressing telomere SCE only under short-telomere conditions.

    Evidence Fancc-/- crossed to Tert mutants, telomere CO-FISH, and serial transplantation

    PMID:20022886

    Open questions at the time
    • Mechanism linking FANCC to telomere recombination unknown
    • Relationship to core complex function unclear
  21. 2013 Medium

    Showing HELQ acts in parallel to FANCC for chromosome stability, while leaving FANCD2 monoubiquitination intact, further dissected FANCC's pathway boundaries.

    Evidence Mouse double-mutant genetics with micronuclei/53BP1 and monoubiquitination assays

    PMID:24005041

    Open questions at the time
    • Molecular interface between the two pathways undefined
    • Single lab
  22. 2014 Medium

    Synergy between dormant-origin loss and FANCC deficiency placed FANCC function in replication fork progression and protection.

    Evidence Mcm4chaos3;Fancc-/- mouse genetics with fork markers and instability/tumorigenesis assays

    PMID:24589582

    Open questions at the time
    • Direct fork-protection mechanism for FANCC not demonstrated
    • Single lab
  23. 2020 Medium

    Identifying FANCC as required for selective autophagy and an anti-ZIKV factor extended its functions beyond repair and apoptosis.

    Evidence Gain/loss-of-function in neural stem cells, Fancc KO mice, E2F4 bioinformatics, and autophagy/viral-titer readouts

    PMID:33073500

    Open questions at the time
    • Molecular mechanism of FANCC in autophagy machinery undefined
    • Relationship to canonical FA roles unclear
  24. 2022 Medium

    Linking FANCC loss to microglial pyroptosis via p38/NLRP3 broadened its anti-cell-death role to inflammatory injury contexts.

    Evidence shRNA/overexpression in a mouse spinal cord injury model with pyroptosis, apoptosis, and behavioral readouts

    PMID:35659106

    Open questions at the time
    • No direct biochemical reconstitution of FANCC-p38/NLRP3 link
    • Whether effect is core-complex dependent unknown
  25. 2023 Medium

    Demonstrating a conserved FANCC-FANCE-FANCF subcomplex acting as an anti-crossover factor in meiosis defined an evolutionarily ancient recombination-regulatory role.

    Evidence Arabidopsis genetic screen, double/triple-mutant epistasis with MUS81, and interaction assays

    PMID:36652992

    Open questions at the time
    • Mechanism of crossover suppression undefined
    • Conservation of meiotic role in mammals not shown in this corpus

Open questions

Synthesis pass · forward-looking unresolved questions
  • How FANCC's cytoplasmic anti-apoptotic/signaling activities and its nuclear core-complex repair function are coordinated within a single cell, and the relative physiological weight of each branch, remains unresolved.
  • No structural model of FANCC or its complexes in this corpus
  • No direct enzymatic activity assigned to FANCC
  • Integration of repair, apoptosis, autophagy, and meiotic roles not unified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 5 GO:0005829 cytosol 2
Pathway
R-HSA-5357801 Programmed Cell Death 3 R-HSA-73894 DNA Repair 3 R-HSA-162582 Signal Transduction 2 R-HSA-1474165 Reproduction 1 R-HSA-9612973 Autophagy 1
Partners
EIF2AK2FANCAFANCEFANCFFANCGHSPA1APORSTAT1
Complex memberships
FANCC-FANCE-FANCD2 ternary complexFANCC-FANCE-FANCF anti-crossover subcomplexFANCC-Hsp70-PKR ternary complexFanconi anemia core complex (FANCA-FANCC-FANCE-FANCF-FANCG)

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 The FACC polypeptide localizes predominantly to the cytoplasm, as determined by cell fractionation and immunofluorescence; it is a 60-kDa protein, and FA group C cell lines express full-length, truncated, or no detectable FACC polypeptide. Two FACC-related proteins (FRP-50 and FRP-150) were also co-immunoprecipitated. Cell fractionation, immunofluorescence, immunoprecipitation with polyclonal antiserum Proceedings of the National Academy of Sciences of the United States of America High 7517562
1996 Cytoplasmic localization of the FAC protein is essential for its functional activity: cytoplasmic isoforms of FAC corrected both the DNA cross-linking defect and enhanced cytotoxicity in FA group C cells, whereas a nucleus-targeted isoform did not correct these phenotypes. Targeted localization constructs (nuclear export/localization signal fusion), functional complementation assay (MMC sensitivity, interstrand cross-link induction) The Journal of clinical investigation High 8621788
1997 FAA (FANCA) and FAC (FANCC) proteins bind each other and form a complex. While unbound FAA and FAC are predominantly cytoplasmic, the FAA-FAC complex is found in both cytoplasm and nucleus. A patient-derived mutant FAC (L554P) fails to bind FAA. Co-immunoprecipitation, subcellular fractionation Nature genetics High 9398857
1997 The FAC protein coimmunoprecipitates with the cyclin-dependent kinase cdc2. FAC expression increases during S phase, peaks at G2/M transition, and declines during M phase. The L554P patient-derived mutant FAC fails to bind cdc2, and the cdc2-binding region maps to the carboxyl-terminal 50 amino acids of FAC. Co-immunoprecipitation, cell synchronization/western blot, deletion mapping Blood Medium 9242535
1997 FA-C lymphoblasts treated with low-dose MMC exhibit prolonged G2/M arrest associated with sustained inactivation of the cyclin B1/cdc2 kinase complex (sustained cyclin B1 accumulation and cdc2 tyrosine phosphorylation), whereas FAC-corrected cells show only transient inactivation. This implicates FAC in a cross-link damage avoidance pathway that signals to the cyclin B/cdc2 kinase. Cell cycle analysis, western blot for cyclin B1 and phospho-cdc2, caffeine-rescue experiment in isogenic FA-C vs. corrected cell lines Cancer research Medium 9187128
1998 FAC protein binds to NADPH cytochrome P450 reductase (RED) in COS-1 and murine liver cells. This interaction requires the amino-terminal region of FAC and the cytosolic FMN-binding domain of RED. FAC expression suppresses RED-mediated reduction of cytochrome c, indicating FAC attenuates RED enzymatic activity. Co-immunoprecipitation, GST pulldown, functional enzymatic assay (cytochrome c reduction), FMN competition assay Blood Medium 9787138
1998 Functional activity of FANCA requires both FAC binding and nuclear localization. Mutation/deletion of the FANCA NLS abolishes FAC binding and nuclear localization; wild-type FAC promotes nuclear accumulation of FAA, and FAA promotes nuclear accumulation of FAC. Mutant FAA forms that fail to bind FAC also fail to support nuclear FAC accumulation. Mutagenesis of NLS, heterologous NLS substitution, co-immunoprecipitation, subcellular fractionation, functional complementation (MMC resistance) Molecular and cellular biology High 9742112
1998 FAA and FAC protect against cross-linker cytotoxicity from different subcellular compartments: nuclear localization of FAA is necessary and sufficient to correct MMC sensitivity in FA-A cells, whereas cytoplasmic FAC is required for its activity. No interaction between FAA and FAC was detected either in vivo or in vitro in this study. Nuclear export/localization signal fusion constructs, subcellular fractionation, co-immunoprecipitation (negative result for FAA-FAC interaction), MMC sensitivity assay Blood Medium 9746759
1998 The FAA/FAC protein complex undergoes nuclear accumulation in a phosphorylation-dependent manner. FA cells from complementation groups A, B, C, E, F, G, and H are all defective in FAA/FAC complex formation, FAA phosphorylation, and nuclear accumulation of the complex, defining a common FA signaling pathway. Western blot, co-immunoprecipitation, subcellular fractionation across multiple FA complementation group cell lines Proceedings of the National Academy of Sciences of the United States of America Medium 9789045
1999 FANCG/XRCC9 is required for binding of FANCA and FANCC proteins. FANCG is a component of the nuclear FANCA-FANCC complex. The amino-terminal region of FANCA is required for FANCG binding, FANCC binding, nuclear localization, and functional activity. Disruption of this tripartite complex results in the FA cellular phenotype. Co-immunoprecipitation, nuclear fractionation, deletion analysis of FANCA, functional complementation assay Molecular and cellular biology High 10373536
1999 Human alpha spectrin II (alphaSpIISigma*) forms a nuclear complex with FANCA and FANCC. Levels of alphaSpIISigma* are reduced in FA-A, FA-B, FA-C, and FA-D cells, suggesting FA proteins contribute to its stability/expression in the nucleus. Co-immunoprecipitation, nuclear fractionation, western blot across FA complementation group cell lines The Journal of biological chemistry Medium 10551855
2000 FANCF forms a nuclear complex with FANCA, FANCC, and FANCG in human lymphoblasts. FANCF is predominantly nuclear. These interactions require each of the FA proteins (A, C, F, G) except FANCD. Loss of any single FA protein (except D) disrupts the nuclear complex. Co-immunoprecipitation, subcellular fractionation, immunofluorescence in multiple FA complementation group cell lines Human molecular genetics High 11063725
2000 FANCC binds STAT1 (preferentially non-phosphorylated STAT1) and facilitates its docking at the IFN-gamma receptor alpha chain, enabling STAT1 phosphorylation. GST-fusion FANCC, but not mutant FANCC (L554P), binds STAT1 in cell lysates. Loss of FANCC results in defective STAT1 docking at the IFN-gammaR, corrected by FANCC transduction. GST pulldown, co-immunoprecipitation, gene transduction rescue, kinetic binding studies Molecular and cellular biology High 10848598
2000 FANCC protein expression is regulated posttranscriptionally in a cell cycle-dependent manner: FANCC protein is lowest at G1/S and highest in M phase, while mRNA levels are constant throughout the cell cycle. This regulation is proteasome-dependent and is encoded within the FANCC coding sequence. Cell synchronization, western blot, mRNA quantification, deletion constructs, proteasome inhibitor treatment Blood Medium 10845936
2001 FANCC interacts with the molecular chaperone Hsp70 via the ATPase domain of Hsp70 and the central 320 residues of FANCC; both Hsp40 and ATP/ADP are required. This FANCC-Hsp70 interaction protects hematopoietic cells from IFN-gamma/TNF-alpha-induced cytotoxicity. Alanine mutations in the Hsp70-interacting domain of FANCC block both Hsp70 binding and cytoprotection. GST pulldown, co-immunoprecipitation, in vitro binding assay, site-directed mutagenesis, cytotoxicity assay The EMBO journal High 11500375
2001 FANCA, FANCC, and FANCG proteins bind to DNA containing psoralen interstrand cross-links, as shown by DNA affinity chromatography from HeLa cell nuclear extracts. DNA affinity chromatography with psoralen cross-linked DNA Biochemistry Medium 11401546
2002 FANCC inhibits PKR (double-stranded RNA-dependent protein kinase) activity both in vivo and in vitro; this requires a physical interaction between FANCC and Hsp70, but not interactions with other Fanconi proteins. FANCC, Hsp70, and PKR form a ternary complex in lymphoblasts and in yeast expressing PKR. FANCC can exert this anti-apoptotic function independently of the FA multiprotein complex. In vitro kinase assay, co-immunoprecipitation (mammalian and yeast cells), yeast expression system (no FA orthologs present), functional survival assay The Journal of biological chemistry High 12397061
2002 FANCE promotes nuclear accumulation of FANCC and is required for FANCA-FANCC complex formation, FANCD2 monoubiquitination, and FANCD2 nuclear foci formation. HA-tagged FANCE coimmunoprecipitates with FANCA, FANCC, and FANCG but not FANCD2 in normal cells. Retroviral transduction rescue, co-immunoprecipitation, immunofluorescence, nuclear fractionation Blood High 12239156
2004 FANCC promotes homologous recombination (HR) repair and also facilitates error-prone repair of endogenously generated abasic sites (via translesion synthesis/mutagenic repair). Efficient repair of cross-links in DT40 cells requires combined functions of FANCC, translesion synthesis, and HR. Loss of FANCC elevates spontaneous sister chromatid exchange (SCE) approximately 2-fold. Gene disruption in DT40 cells, sister chromatid exchange assay, epistasis analysis with TLS and HR mutants, survival assays Molecular cell High 15327776
2004 FANCC deficiency in DT40 cells elevates spontaneous SCE ~2-fold, requiring XRCC3 (HR factor). FANCC loss combined with RAD18 loss (TLS) yields more SCE than either single mutant (non-epistatic). FANCC is functionally linked to BLM helicase: the fancc/blm double mutant has similar SCE to blm alone, and MMC-induced BLM nuclear foci formation is severely reduced in fancc or fancd2 cells. Gene disruption and double-mutant analysis in DT40 cells, SCE assay, GFP-BLM nuclear focus formation, cell survival assays The EMBO journal High 15616572
2005 FANCC, FANCE, and FANCD2 form a ternary complex: FANCE mediates the interaction between FANCC and FANCD2. FANCE mutants that interact with FANCC but not FANCD2 abrogate FANCD2 monoubiquitination and fail to complement FA-E cells. FANCE also mediates the interaction between FANCC and FANCF within the core complex. Yeast two-hybrid and three-hybrid systems, co-immunoprecipitation in human cells, random mutagenesis screen, functional complementation (FANCD2 monoubiquitination, MMC resistance) The Journal of biological chemistry High 16127171
2006 FANCC disruption abrogates FANCD2 monoubiquitination, confirming impaired FA pathway function. FANCC-deficient cancer cells show increased G2/M arrest and clastogenic damage in response to DNA interstrand cross-linking agents, but not gemcitabine, etoposide, or hydrogen peroxide. FANCC disruption also increases spontaneous chromosomal breakage. Targeted endogenous gene disruption in human adenocarcinoma cells, FANCD2 monoubiquitination assay, drug sensitivity assays, cytogenetic analysis Gastroenterology Medium 16762635
2006 FANCE nuclear accumulation depends specifically on FANCC: other FA proteins are not involved in FANCE nuclear localization. The FANCE region interacting with FANCC is distinct from the region binding FANCD2, supporting a model where FANCE recruits FANCD2 to the core complex independently of FANCC binding. Co-immunoprecipitation, subcellular fractionation, nuclear export signal fusion constructs, FA mutant cell complementation DNA repair Medium 16513431
2006 Epistasis analysis in DT40 cells shows FANCC (FA core complex) and BRCA2 CTD are epistatic for X-ray sensitivity, but FANCC and BRCA2 CTD act in parallel pathways for interstrand cross-link repair. BRCA2-dependent Rad51 chromatin loading after MMC is not compromised by loss of FANCC or FANCD2. Gene disruption and double-mutant analysis in DT40 cells, survival assays (X-ray, cisplatin, MMC), chromosomal aberration analysis, immunofluorescence for Rad51 and FancD2 foci The Journal of biological chemistry Medium 16687415
2009 FANCC suppresses telomere sister chromatid exchange (T-SCE) specifically when telomeres are short: Fancc deficiency increases T-SCE incidence in mice crossed into a short-telomere background (Tert+/- or Tert-/-), but not in mice with long telomeres. Fancc deficiency also accelerates telomere attrition during high-turnover hematopoietic cell transplantation. Mouse genetics (Fancc-/- crossed to Tert mutants), telomere FISH/CO-FISH, serial transplantation assay Human molecular genetics Medium 20022886
2013 HELQ operates in parallel to (non-epistatic with) FANCC for suppression of spontaneous chromosome instability: Helq/Fancc double mutant mice show substantially worse phenotypes (micronuclei, 53BP1 nuclear bodies) than either single mutant. Unlike Fancc-/- cells, Helq mutant cells retain intact FANCD2 monoubiquitination and focus formation. Mouse double-mutant genetics, FANCD2 monoubiquitination assay, micronuclei/53BP1 nuclear body quantification, MMC sensitivity assay Nucleic acids research Medium 24005041
2014 Combined loss of dormant replication origins (Mcm4chaos3) and FANCC results in synergistic increases in stalled/collapsed replication fork markers and genome instability beyond either single mutant, identifying an important functional overlap between dormant origins and the FA pathway in maintaining fork progression. Mouse double-mutant genetics (Mcm4chaos3;Fancc-/-), replication fork markers, genome instability assays, tumorigenesis analysis Nucleic acids research Medium 24589582
2020 ZIKV downregulates FANCC (via suppression of transcription factor E2F4) to evade selective autophagy and enhance viral replication. FANCC is essential for selective autophagy and acts as a negative regulator of ZIKV replication; Fancc KO mice show increased ZIKV infection. Gain/loss-of-function assays in neural stem cells, Fancc KO mouse model, bioinformatics (E2F4 identification), autophagy marker western blot, viral titer measurement EMBO reports Medium 33073500
2022 FANCC deficiency promotes microglial pyroptosis via the p38/NLRP3 pathway, leading to secondary neuronal apoptosis in spinal cord injury. Overexpression of FANCC suppresses microglial pyroptosis and neuronal apoptosis; knockdown worsens both outcomes. Gain/loss-of-function (shRNA and overexpression) in mouse SCI model, western blot, immunofluorescence, TUNEL, flow cytometry, behavioral assays Cell & bioscience Medium 35659106
2023 The FANCC-FANCE-FANCF subcomplex is evolutionarily conserved from vertebrates to plants and functions as an anti-crossover factor during meiotic recombination. Loss of FANCC, FANCE, or FANCF partially rescues CO-defective mutants; FANCC/FANCE/FANCF mutations cause synthetic meiotic catastrophe with the pro-CO factor MUS81. Genetic screen in Arabidopsis, genetic epistasis (double and triple mutants), co-immunoprecipitation/protein interaction assays, meiotic crossover quantification Nucleic acids research Medium 36652992
1996 FAC protein expression suppresses apoptosis induced by growth factor withdrawal in hematopoietic factor-dependent progenitor cell lines (32D and MO7e), promoting increased viability rather than proliferation, consistent with an anti-apoptotic function analogous to Bcl-2. Retroviral-mediated gene transfer, flow cytometry (propidium iodide), morphologic analysis in factor-deprived cells Blood Medium 8977247
1996 Antisense oligonucleotide-mediated repression of FACC gene expression in normal human bone marrow cells inhibits clonal growth of erythroid and granulocyte-macrophage progenitors in a sequence-specific fashion, establishing a direct role for FACC in hematopoietic progenitor cell growth/survival. Antisense oligodeoxynucleotide treatment, colony-forming assay, mRNA quantification, mitomycin C sensitivity assay The Journal of clinical investigation Medium 7518843
2004 Type I IFN-induced activation of STAT1, STAT3, and STAT5, as well as TYK2 and JAK1 phosphorylation, is impaired in FA-C cells bearing FANCC-inactivating mutations. This is accompanied by reduced Th1 (IFN-gamma-producing CD4+) differentiation in Fancc null mice. Western blot for phospho-STATs and kinases, flow cytometry of T cell subsets, cytokine secretion assay in Fancc-/- mice Journal of immunology Medium 15356134
1993 A leucine-to-proline substitution at codon 554 (L554P) completely abolishes FACC protein functional complementing activity, confirming that FACC encodes a ~60 kDa protein required for resistance to DNA cross-linking agents. Site-directed mutagenesis, functional complementation assay (MMC sensitivity) Human molecular genetics Medium 8499901

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 Evidence for at least four Fanconi anaemia genes including FACC on chromosome 9. Nature genetics 292 1303234
2004 The Fanconi anaemia gene FANCC promotes homologous recombination and error-prone DNA repair. Molecular cell 253 15327776
1996 Inactivation of Fac in mice produces inducible chromosomal instability and reduced fertility reminiscent of Fanconi anaemia. Nature genetics 210 8630504
1999 Fanconi anemia proteins FANCA, FANCC, and FANCG/XRCC9 interact in a functional nuclear complex. Molecular and cellular biology 195 10373536
2012 Exome sequencing identifies rare deleterious mutations in DNA repair genes FANCC and BLM as potential breast cancer susceptibility alleles. PLoS genetics 168 23028338
2000 The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG. Human molecular genetics 167 11063725
1997 The Fanconi anaemia proteins, FAA and FAC, interact to form a nuclear complex. Nature genetics 154 9398857
1998 Multiple inhibitory cytokines induce deregulated progenitor growth and apoptosis in hematopoietic cells from Fac-/- mice. Blood 147 9596654
1993 A common mutation in the FACC gene causes Fanconi anaemia in Ashkenazi Jews. Nature genetics 135 8348157
1999 Loss of FancC function results in decreased hematopoietic stem cell repopulating ability. Blood 129 10381491
1998 Abnormal microsomal detoxification implicated in Fanconi anemia group C by interaction of the FAC protein with NADPH cytochrome P450 reductase. Blood 123 9787138
1994 The Fanconi anemia polypeptide FACC is localized to the cytoplasm. Proceedings of the National Academy of Sciences of the United States of America 123 7517562
2007 Rhenium fac tricarbonyl bisimine complexes: biologically useful fluorochromes for cell imaging applications. Chemical communications (Cambridge, England) 122 17639143
1994 Mutation analysis of the Fanconi anemia gene FACC. American journal of human genetics 121 8128956
2001 FANCC interacts with Hsp70 to protect hematopoietic cells from IFN-gamma/TNF-alpha-mediated cytotoxicity. The EMBO journal 116 11500375
1998 Functional activity of the fanconi anemia protein FAA requires FAC binding and nuclear localization. Molecular and cellular biology 108 9742112
1998 The fanconi anemia pathway requires FAA phosphorylation and FAA/FAC nuclear accumulation. Proceedings of the National Academy of Sciences of the United States of America 105 9789045
1999 Engraftment of hematopoietic progenitor cells transduced with the Fanconi anemia group C gene (FANCC). Human gene therapy 104 10515453
2004 Functional relationships of FANCC to homologous recombination, translesion synthesis, and BLM. The EMBO journal 99 15616572
2000 The Fanconi anemia protein FANCC binds to and facilitates the activation of STAT1 by gamma interferon and hematopoietic growth factors. Molecular and cellular biology 94 10848598
2019 Streamlined Protocol for Deep Proteomic Profiling of FAC-sorted Cells and Its Application to Freshly Isolated Murine Immune Cells. Molecular & cellular proteomics : MCP 93 30792265
1997 Phenotypic consequences of mutations in the Fanconi anemia FAC gene: an International Fanconi Anemia Registry study. Blood 87 9207444
1997 The Fanconi anemia polypeptide, FAC, binds to the cyclin-dependent kinase, cdc2. Blood 85 9242535
1995 Carrier frequency of the IVS4 + 4 A-->T mutation of the Fanconi anemia gene FAC in the Ashkenazi Jewish population. Blood 85 7492758
2002 The anti-apoptotic function of Hsp70 in the interferon-inducible double-stranded RNA-dependent protein kinase-mediated death signaling pathway requires the Fanconi anemia protein, FANCC. The Journal of biological chemistry 80 12397061
2007 HER2 expression and efficacy of preoperative paclitaxel/FAC chemotherapy in breast cancer. Breast cancer research and treatment 78 17468948
1999 Human alpha spectrin II and the Fanconi anemia proteins FANCA and FANCC interact to form a nuclear complex. The Journal of biological chemistry 76 10551855
1996 Suppression of apoptosis in hematopoietic factor-dependent progenitor cell lines by expression of the FAC gene. Blood 76 8977247
2014 Ligand functionalization as a deactivation pathway in a fac-Ir(ppy)3-mediated radical addition. Chemical science 69 28706624
2002 The Fanconi anemia protein, FANCE, promotes the nuclear accumulation of FANCC. Blood 69 12239156
2001 Defective hematopoiesis and hepatic steatosis in mice with combined deficiencies of the genes encoding Fancc and Cu/Zn superoxide dismutase. Blood 69 11493445
2002 Retroviral-mediated expression of recombinant Fancc enhances the repopulating ability of Fancc-/- hematopoietic stem cells and decreases the risk of clonal evolution. Blood 68 12393504
2001 Human alpha spectrin II and the FANCA, FANCC, and FANCG proteins bind to DNA containing psoralen interstrand cross-links. Biochemistry 67 11401546
2008 Alterations in candidate genes PHF2, FANCC, PTCH1 and XPA at chromosomal 9q22.3 region: pathological significance in early- and late-onset breast carcinoma. Molecular cancer 66 18990233
2007 Inflammatory reactive oxygen species-mediated hemopoietic suppression in Fancc-deficient mice. Journal of immunology (Baltimore, Md. : 1950) 64 17404312
2004 The genetics of FANCC and FANCG in familial pancreatic cancer. Cancer biology & therapy 62 14726700
2005 Frontal affinity chromatography with MS detection (FAC-MS) in drug discovery. Drug discovery today 60 15808820
2010 Uptake and localisation of rhenium fac-tricarbonyl polypyridyls in fluorescent cell imaging experiments. Organic & biomolecular chemistry 58 20593068
1996 Cytoplasmic localization of FAC is essential for the correction of a prerepair defect in Fanconi anemia group C cells. The Journal of clinical investigation 57 8621788
1996 The effect of the Fanconi anemia polypeptide, FAC, upon p53 induction and G2 checkpoint regulation. Blood 55 8704210
2010 Correct mRNA processing at a mutant TT splice donor in FANCC ameliorates the clinical phenotype in patients and is enhanced by delivery of suppressor U1 snRNAs. American journal of human genetics 50 20869034
2000 The IVS4 + 4 A to T mutation of the fanconi anemia gene FANCC is not associated with a severe phenotype in Japanese patients. Blood 49 10666230
1993 A Leu554-to-Pro substitution completely abolishes the functional complementing activity of the Fanconi anemia (FACC) protein. Human molecular genetics 49 8499901
2011 Complexes in context: attempting to control the cellular uptake and localisation of rhenium fac-tricarbonyl polypyridyl complexes. Dalton transactions (Cambridge, England : 2003) 48 21897946
2006 Targeted disruption of FANCC and FANCG in human cancer provides a preclinical model for specific therapeutic options. Gastroenterology 47 16762635
2004 Continuous in vivo infusion of interferon-gamma (IFN-gamma) preferentially reduces myeloid progenitor numbers and enhances engraftment of syngeneic wild-type cells in Fancc-/- mice. Blood 47 15113761
2012 New insights into the chemistry of fac-[Ru(CO)₃]²⁺ fragments in biologically relevant conditions: the CO releasing activity of [Ru(CO)₃Cl₂(1,3-thiazole)], and the X-ray crystal structure of its adduct with lysozyme. Journal of inorganic biochemistry 46 22883959
2005 Pyrazolyl derivatives as bifunctional chelators for labeling tumor-seeking peptides with the fac-[M(CO)3]+ moiety (M = 99mTc, Re): synthesis, characterization, and biological behavior. Bioconjugate chemistry 46 15769099
2006 Pyrazolyl conjugates of bombesin: a new tridentate ligand framework for the stabilization of fac-[M(CO)3]+ moiety. Nuclear medicine and biology 45 16843837
1998 The Fanconi anemia proteins FAA and FAC function in different cellular compartments to protect against cross-linking agent cytotoxicity. Blood 45 9746759
2016 The Flint Animal Cancer Center (FACC) Canine Tumour Cell Line Panel: a resource for veterinary drug discovery, comparative oncology and translational medicine. Veterinary and comparative oncology 43 27197945
1998 Overexpression of the fanconi anemia group C gene (FAC) protects hematopoietic progenitors from death induced by Fas-mediated apoptosis. Cancer research 42 9721856
2010 Genetic disruption of both Fancc and Fancg in mice recapitulates the hematopoietic manifestations of Fanconi anemia. Blood 41 20606166
2021 Combination of Simvastatin and FAC Improves Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer. Cancer research and treatment 40 33705623
2020 DHD4, a CONSTANS-like family transcription factor, delays heading date by affecting the formation of the FAC complex in rice. Molecular plant 40 33246053
2010 SuperSAGE analysis of the Nicotiana attenuata transcriptome after fatty acid-amino acid elicitation (FAC): identification of early mediators of insect responses. BMC plant biology 40 20398280
2005 Ultrafast excited-state dynamics preceding a ligand trans-cis isomerization of fac-[Re(Cl)(CO)3(t-4-styrylpyridine)2] and fac-[Re(t-4-styrylpyridine)(CO)3(2,2'-bipyridine)]+. The journal of physical chemistry. A 40 16833623
2008 Melanoma targeting with alpha-melanocyte stimulating hormone analogs labeled with fac-[99mTc(CO)3]+: effect of cyclization on tumor-seeking properties. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry 39 18183429
2015 Genetic variants associated with risk of atrial fibrillation regulate expression of PITX2, CAV1, MYOZ1, C9orf3 and FANCC. Journal of molecular and cellular cardiology 38 26073630
1994 Repression of Fanconi anemia gene (FACC) expression inhibits growth of hematopoietic progenitor cells. The Journal of clinical investigation 38 7518843
2001 Functional correction of FA-C cells with FANCC suppresses the expression of interferon gamma-inducible genes. Blood 37 11342426
2011 Association of FANCC and PTCH1 with the development of early dysplastic lesions of the head and neck. Annals of surgical oncology 35 21861228
2013 Helq acts in parallel to Fancc to suppress replication-associated genome instability. Nucleic acids research 34 24005041
1998 The facC gene of Aspergillus nidulans encodes an acetate-inducible carnitine acetyltransferase. Journal of bacteriology 34 9829933
1997 VACTERL with hydrocephalus in twins due to Fanconi anemia (FA): mutation in the FAC gene. American journal of medical genetics 34 8986283
2006 Functional interplay between BRCA2/FancD1 and FancC in DNA repair. The Journal of biological chemistry 33 16687415
2005 FANCC, FANCE, and FANCD2 form a ternary complex essential to the integrity of the Fanconi anemia DNA damage response pathway. The Journal of biological chemistry 33 16127171
2008 Hypermethylation of the FANCC and FANCL promoter regions in sporadic acute leukaemia. Cellular oncology : the official journal of the International Society for Cellular Oncology 32 18607065
2015 The risk for developing cancer in Israeli ATM, BLM, and FANCC heterozygous mutation carriers. Cancer genetics 31 26778106
2012 p38 MAPK inhibition suppresses the TLR-hypersensitive phenotype in FANCC- and FANCA-deficient mononuclear phagocytes. Blood 31 22234699
1996 Developmental expression of the Fac gene correlates with congenital defects in Fanconi anemia patients. Human molecular genetics 31 8789444
2005 Guanine and plasmid DNA binding of mono- and trinuclear fac-[Re(CO)3]+ complexes with amino acid ligands. Chembiochem : a European journal of chemical biology 30 15959921
1997 Involvement of the Fanconi's anemia protein FAC in a pathway that signals to the cyclin B/cdc2 kinase. Cancer research 30 9187128
2013 FANCA and FANCC modulate TLR and p38 MAPK-dependent expression of IL-1β in macrophages. Blood 29 24046015
2003 Synthesis of 17-alpha-substituted estradiol-pyridin-2-yl hydrazine conjugates as effective ligands for labeling with Alberto's complex fac-[Re(OH2)3(CO)3]+ in water. The Journal of organic chemistry 29 12946150
2022 FANCC deficiency mediates microglial pyroptosis and secondary neuronal apoptosis in spinal cord contusion. Cell & bioscience 28 35659106
2014 A concomitant loss of dormant origins and FANCC exacerbates genome instability by impairing DNA replication fork progression. Nucleic acids research 28 24589582
2018 Identification of the First Diketomorpholine Biosynthetic Pathway Using FAC-MS Technology. ACS chemical biology 27 29631395
2008 Overnight transduction with foamyviral vectors restores the long-term repopulating activity of Fancc-/- stem cells. Blood 27 18684868
2000 Strong FANCA/FANCG but weak FANCA/FANCC interaction in the yeast 2-hybrid system. Blood 27 10627486
2014 Clickable, hydrophilic ligand for fac-[M(I)(CO)3](+) (M = Re/(99m)Tc) applied in an S-functionalized α-MSH peptide. Bioconjugate chemistry 26 24568284
2009 FANCC suppresses short telomere-initiated telomere sister chromatid exchange. Human molecular genetics 26 20022886
2005 Synthesis, characterization and antiproliferative behavior of tricarbonyl complexes of rhenium(I) with some 6-amino-5-nitrosouracil derivatives: crystal structure of fac-[ReCl(CO)3(DANU-N5,O4)] (DANU=6-amino-1,3-dimethyl-5-nitrosouracil). Journal of inorganic biochemistry 26 15964633
1995 Short-course FAC-M versus 1 year of CMFVP in node-positive, hormone receptor-negative breast cancer: an intergroup study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 26 7707108
2020 Zika virus depletes neural stem cells and evades selective autophagy by suppressing the Fanconi anemia protein FANCC. EMBO reports 25 33073500
2010 Genetic inactivation of the Fanconi anemia gene FANCC identified in the hepatocellular carcinoma cell line HuH-7 confers sensitivity towards DNA-interstrand crosslinking agents. Molecular cancer 25 20509860
2004 Impaired type I IFN-induced Jak/STAT signaling in FA-C cells and abnormal CD4+ Th cell subsets in Fancc-/- mice. Journal of immunology (Baltimore, Md. : 1950) 23 15356134
2000 Mitomycin C and diepoxybutane action mechanisms and FANCC protein functions: further insights into the role for oxidative stress in Fanconi's anaemia phenotype. Carcinogenesis 23 10783335
2000 Posttranscriptional cell cycle-dependent regulation of human FANCC expression. Blood 23 10845936
2018 Interrogation of Benzomalvin Biosynthesis Using Fungal Artificial Chromosomes with Metabolomic Scoring (FAC-MS): Discovery of a Benzodiazepine Synthase Activity. Biochemistry 22 29533658
2012 Post-protein-binding reactivity and modifications of the fac-[Re(CO)3]+ core. Inorganic chemistry 22 22229733
2010 Cyanide-bridged Fe(III)-Mn(III) bimetallic systems assembled from the fac-Fe tricyanide and Mn Schiff bases: structures, magnetic properties, and density functional theory calculations. Inorganic chemistry 22 20402476
2011 Excited state dependent electron transfer of a rhenium-dipyridophenazine complex intercalated between the base pairs of DNA: a time-resolved UV-visible and IR absorption investigation into the photophysics of fac-[Re(CO)3(F2dppz)(py)]+ bound to either [poly(dA-dT)]2 or [poly(dG-dC)]2. Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology 21 21698328
2007 fac-{Ru(CO)3}2+-core complexes and design of metal-based drugs. synthesis, structure, and reactivity of Ru-thiazole derivative with serum proteins and absorption-release studies with acryloyl and silica hydrogels as carriers in physiological media. Inorganic chemistry 21 17198415
2023 The FANCC-FANCE-FANCF complex is evolutionarily conserved and regulates meiotic recombination. Nucleic acids research 20 36652992
2006 The nuclear accumulation of the Fanconi anemia protein FANCE depends on FANCC. DNA repair 20 16513431
1996 Induction of Fanconi anemia cellular phenotype in human 293 cells by overexpression of a mutant FAC allele. The Journal of clinical investigation 20 8613549
1994 Genetic mapping of the FACC gene and linkage analysis in Fanconi anaemia families. Journal of medical genetics 20 7853372
2015 Array tomography: characterizing FAC-sorted populations of zebrafish immune cells by their 3D ultrastructure. Journal of microscopy 18 25611576
2012 A Dutch Fanconi Anemia FANCC Founder Mutation in Canadian Manitoba Mennonites. Anemia 18 22701786

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