Affinage

FAN1

Fanconi-associated nuclease 1 · UniProt Q9Y2M0

Length
1017 aa
Mass
114.2 kDa
Annotated
2026-06-09
58 papers in source corpus 34 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FAN1 is a structure-specific DNA nuclease that safeguards genome stability during the repair of interstrand crosslinks (ICLs) and the maintenance of trinucleotide repeat tracts (PMID:20603073, PMID:20603015). It combines 5'-3' exonuclease and 5' flap endonuclease activities mediated by an atypical monomeric VRR_nuc domain, whose insertion biases specificity toward 5' flap substrates rather than the Holliday junctions cleaved by its dimeric bacterial/viral homologs (PMID:20603015, PMID:24981866). Mechanistically, FAN1 anchors at a 5'-terminal phosphate at a nick or short flap and incises successively at every third nucleotide, excising one strand around a lesion through flanking incisions, with head-to-tail dimerization positioning and unwinding the substrate for cleavage (PMID:25430771, PMID:25500724). FAN1 is recruited to ICL-stalled forks through its UBZ domain binding monoubiquitinated FANCD2, and this recruitment drives ICL repair (PMID:20603073, PMID:20671156); however, FAN1 also restrains stalled replication fork progression through a FANCD2-dependent but UBZ-independent route, and its nuclease activity controls ploidy during ICL processing, with nuclease-dead mice developing karyomegalic interstitial nephritis and cancer predisposition (PMID:25135477, PMID:26797144, PMID:26980188). Independently of the Fanconi anemia pathway, FAN1 suppresses somatic trinucleotide repeat expansion: it removes extrahelical repeat extrusions via RFC-PCNA-directed, strand-oriented cleavage that competes with pro-expansionary mismatch repair, and it binds MLH1 through an N-terminal SPYF motif to block assembly of expansion-promoting MMR complexes (PMID:31955481, PMID:34330701, PMID:34469738, PMID:37549289, PMID:41145416). This repeat-protective role underlies its modification of Huntington disease, where FAN1 variants that impair DNA binding or nuclease activity hasten disease onset and accelerate CAG expansion (PMID:32589923, PMID:35379994). FAN1 abundance is set by APC/C^Cdh1-mediated degradation and USP7-mediated deubiquitination (PMID:22854063, PMID:41786746).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2010 High

    Established FAN1 as a previously uncharacterized nuclease that physically couples DNA crosslink repair to the Fanconi anemia pathway, answering what enzyme acts downstream of activated FANCD2.

    Evidence shRNA/siRNA screens, in vitro nuclease assays on branched DNA, Co-IP with monoubiquitinated FANCD2, UBZ domain mutants and damage foci across four simultaneous studies

    PMID:20603015 PMID:20603016 PMID:20603073 PMID:20671156

    Open questions at the time
    • Did not resolve the catalytic mechanism of incision
    • Did not define whether ICL repair function requires FA pathway exclusively
  2. 2010 High

    Defined FAN1 damage specificity and localization, showing it acts at stalled replication forks and contributes to ICL processing partly independently of the classical FA pathway.

    Evidence RPA colocalization with UBZ-mutant immunofluorescence; FAN1-null DT40 cells with agent-specific survival and double-mutant epistasis (FANCC, FANCI)

    PMID:20935496 PMID:21115814

    Open questions at the time
    • Mechanistic basis of FA-independent ICL processing unresolved
    • Single-cell-line localization data
  3. 2014 High

    Resolved the structural and catalytic basis of FAN1 incision, explaining how it unhooks ICLs by iterative cleavage and why its VRR_nuc domain favors flaps over junctions.

    Evidence Crystal structures of human and Pseudomonas FAN1 with 5' flap DNA, dimerization assays, active-site and VRR_nuc mutagenesis with nuclease readouts

    PMID:24981866 PMID:25319828 PMID:25430771 PMID:25500724

    Open questions at the time
    • Structures did not capture the FANCD2-bound recruited state
    • In vivo relevance of dimerization not directly tested
  4. 2014 High

    Showed FAN1 has a UBZ-independent role in replication fork protection, distinguishing its fork-stability function from its ICL repair recruitment.

    Evidence Co-IP into a BLM-FANCD2 complex, chromatin fractionation, fork restart assays, MRE11/FANCD2 epistasis, RPA-coated substrate nuclease assays

    PMID:25135477 PMID:25922199

    Open questions at the time
    • How FANCD2 directs FAN1 without the UBZ interaction unclear
    • Single-lab functional data
  5. 2016 High

    Separated FAN1's two genome-protective activities in vivo, demonstrating that Ub-FANCD2-directed fork restraint, not ICL repair, prevents chromosome instability and cancer.

    Evidence Nuclease-dead and UBZ-mutant knockin/knockout mice, fork progression assays, ploidy and karyomegalic nephritis phenotypes, SNM1A and SLX4 epistasis

    PMID:26797144 PMID:26980188 PMID:26980189

    Open questions at the time
    • Tissue-specificity of karyomegalic phenotype not fully explained
    • Redundancy partners beyond SNM1A not enumerated
  6. 2018 Medium

    Identified FAN1 as a suppressor of somatic trinucleotide repeat expansion, opening its role as a Huntington disease and Fragile X modifier.

    Evidence Direct CAG repeat DNA binding assays, repeat expansion measurement in patient-derived cells and Fan1 knockout mice (CAG and CGG models), nuclease-dead mutant tests

    PMID:29990673 PMID:30358836

    Open questions at the time
    • Conflicting evidence on whether nuclease activity is required for repeat protection
    • Mechanism of repeat-specific recognition not defined
  7. 2020 High

    Linked FAN1's repeat-stabilizing activity to MLH1-dependent mismatch repair and to disease-modifying variants, framing the genetic interaction underlying CAG instability.

    Evidence Fan1/Mlh1 double-knockout epistasis in mice, variant DNA-binding and complementation assays (R507H, R377W), FAN1 knockout in HD-iPSCs, O6-methylguanine-induced MLH1 colocalization

    PMID:31955481 PMID:32589923 PMID:32876667

    Open questions at the time
    • Molecular nature of FAN1-MLH1 antagonism not yet structurally defined
    • Whether MLH1 recruits or is restricted by FAN1 still mixed
  8. 2021 High

    Defined the dual mechanism by which FAN1 stabilizes repeats: SPYF-motif binding to MLH1 that blocks pro-expansion MMR assembly, plus nuclease-dependent accurate processing of slip-outs.

    Evidence SPYF motif and S126-phospho mutagenesis, Co-IP and MSH3 competition assays, slip-out cleavage mapping, nuclease-dead knockin mice with EXO1/FANCD2 epistasis

    PMID:34330701 PMID:34469738 PMID:34718701 PMID:34879276

    Open questions at the time
    • How phospho-regulation of the MLH1 interaction is coordinated with cell cycle and damage not fully mapped
    • Relative contribution of nuclease vs MLH1-blocking arms in vivo unquantified
  9. 2023 High

    Revealed that RFC-PCNA confers strand directionality to FAN1, providing the biochemical mechanism for extrusion removal that competes with expansion-driving MMR.

    Evidence Reconstituted in vitro nuclease assays on extrusion substrates, PCNA/RFC activation and FAN1-PCNA interaction assays, cell-extract extrusion removal

    PMID:37549289

    Open questions at the time
    • In vivo requirement of PCNA interaction not yet shown in animals
    • Coupling to downstream resynthesis only partly defined
  10. 2025 High

    Provided structural and reconstituted-pathway resolution of the FAN1-PCNA repeat-contraction machine and connected it to the disease-modifying R507H variant.

    Evidence Cryo-EM of FAN1-PCNA-DNA ternary complex (two independent groups), R507/PCNA-D232 interface mutants, reconstituted contraction assay with Pol-delta and MutL-gamma inhibition

    PMID:40368883 PMID:40368897 PMID:41145416

    Open questions at the time
    • Cellular validation of MutL-gamma inhibition pending
    • How extrusion cleavage integrates with full MMR opposition in vivo unresolved
  11. 2026 Medium

    Established that FAN1 protein abundance is actively controlled by deubiquitination, linking FAN1 stability to both ICL resistance and repeat instability.

    Evidence FAN1-USP7 Co-IP, proteasome-inhibitor stability assays, chromatin fractionation, ICL sensitivity and CAG expansion phenotypes upon USP7 depletion

    PMID:41786746

    Open questions at the time
    • Single-lab study without reciprocal in vivo validation
    • Interplay between USP7 stabilization and APC/C^Cdh1 degradation not directly tested
  12. 2022 Medium

    Connected FAN1 loss to a defined disease pathology, showing persistent damage drives replication-factor-dependent polyploidization in kidney tubules.

    Evidence Fan1 knockout mice, CDT1/CDC6 expression analysis, Roscovitine pharmacological rescue of tubular injury

    PMID:35931300

    Open questions at the time
    • Direct link between FAN1 nuclease activity and CDT1/CDC6 dysregulation not established
    • Single-model mechanistic data

Open questions

Synthesis pass · forward-looking unresolved questions
  • How FAN1 selects between its ICL-repair, fork-protection, and repeat-stabilization functions, and how its regulators temporally coordinate these activities, remains unresolved.
  • No unified model coordinating UBZ-dependent vs UBZ-independent recruitment
  • Cell-cycle and phospho-regulatory switching between MLH1 and FANCD2 partners not mapped
  • In vivo balance of degradation (APC/C) vs stabilization (USP7) untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 8 GO:0016787 hydrolase activity 4 GO:0003677 DNA binding 3
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 1
Pathway
R-HSA-73894 DNA Repair 4 R-HSA-1643685 Disease 3 R-HSA-69306 DNA Replication 2
Partners
BLMFANCD2MLH1MSH3PCNARFCUSP7

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 FAN1 (KIAA1018) possesses intrinsic 5'-3' exonuclease activity and endonuclease activity that cleaves nicked and branched DNA structures, and is recruited to sites of DNA damage through its UBZ (ubiquitin-binding zinc finger) domain binding to monoubiquitinated FANCD2, colocalizing with the FANCI-FANCD2 complex at ICL damage sites. shRNA screen, in vitro nuclease assays, colocalization/foci analysis, domain mutant analysis Molecular cell High 20603073
2010 FAN1 (KIAA1018/MTMR15) interacts with and is recruited to DNA damage sites by the monoubiquitinated form of FANCD2; it exhibits endonuclease activity toward 5' flaps and 5' exonuclease activity mediated by a VRR_nuc domain; depletion causes hypersensitivity to ICLs and genome instability. Protein interaction (Co-IP/pulldown), in vitro nuclease assays, siRNA knockdown, DNA damage foci Cell High 20603015
2010 FAN1 (KIAA1018) is a 5'→3' exonuclease and structure-specific endonuclease that preferentially incises 5' flaps; its N-terminal UBZ domain interacts with monoubiquitylated FANCD2 to enable recruitment to DNA damage; depletion sensitizes cells to ICL-inducing agents and causes chromosomal instability. In vitro nuclease assays, Co-IP/pulldown with ubiquitinated FANCD2, siRNA knockdown, chromosomal instability assay Cell High 20603016
2010 FAN1 promotes ICL repair in a manner strictly dependent on its ability to accumulate at sites of DNA damage, relying on monoubiquitylation of the FANCI-FANCD2 complex for recruitment. Cell-based ICL repair assay, localization studies, epistasis with FANCD2 monoubiquitination Science High 20671156
2010 FAN1 is a nuclear protein that forms DNA-damage-induced foci at stalled replication forks (as marked by RPA colocalization); localization to damage sites is dependent on its UBZ domain. Immunofluorescence, colocalization with RPA, UBZ domain mutant analysis, RNAi knockdown Cell cycle Medium 20935496
2010 FAN1-null DT40 chicken cells are highly sensitive to cisplatin and MMC but not to IR, UV, MMS, or camptothecin; cells lacking both FAN1 and FANCC or FANCI showed increased cisplatin sensitivity compared to single knockouts, suggesting FAN1 participates in ICL processing independently of the classical FA pathway in addition to its FA-associated role. Gene targeting (knockout), survival assay, epistasis analysis (double mutant) PNAS High 21115814
2014 Crystal structures of human FAN1 in complex with 5' flap DNA reveal that FAN1 cleaves DNA successively at every third nucleotide via an exonuclease mechanism; this requires a 5'-terminal phosphate anchor at a nick or 1–2 nucleotide flap; this mechanism allows FAN1 to excise an ICL from one strand through flanking incisions. X-ray crystallography, in vitro biochemical assays with mutant analysis Science High 25430771
2014 Crystal structures of human FAN1 with 5' flap DNA show two FAN1 molecules form a head-to-tail dimer that locates the lesion, orients the DNA, and unwinds a 5' flap for subsequent incision; mutations disrupting dimerization, substrate orientation, or flap unwinding impair nuclease activity. X-ray crystallography, in vitro nuclease assay, structure-informed mutagenesis Nature communications High 25500724
2014 FAN1 activity on asymmetric repair intermediates is mediated by an atypical monomeric VRR_nuc domain; unlike the dimeric bacterial/viral VRR_nuc homologs (which cleave Holliday junctions), FAN1's VRR_nuc contains an insertion that prevents dimerization and biases specificity toward 5' flap structures. Crystal structure of VRR_nuc domains, solution dimerization assays, nuclease activity assays Cell reports High 24981866
2014 Crystal structure of Pseudomonas aeruginosa FAN1 (ortholog) bound to 5' flap DNA reveals all four protein domains participate in DNA recognition; a six-helix bundle connects to the VRR_nuc catalytic domain and positions the scissile phosphate for incision; the six-helix bundle also inhibits cleavage of intact Holliday junctions. X-ray crystallography, in vitro nuclease assays, domain mutagenesis Genes & development High 25319828
2014 FAN1 is recruited to aphidicolin (APH)-stalled replication forks by joining a BLM-FANCD2 complex in an MRE11- and FANCD2-dependent manner; FAN1 nuclease activity is required for fork restart; this recruitment occurs independently of the FA core complex or the FAN1 UBZ domain. In the absence of FANCD2, MRE11 promotes aberrant FAN1 access to stalled forks resulting in nucleolytic degradation of nascent DNA. Co-IP, chromatin fractionation, fork restart assay, mutant cell lines, epistasis Molecular and cellular biology High 25135477
2015 FAN1 efficiently promotes strand incision on RPA-coated 5'-flapped DNA substrates; RPA coating does not block but rather supports FAN1-mediated incision at the proper site. In vitro nuclease assay with purified recombinant human FAN1 and RPA on 5'-flap DNA substrates Journal of biochemistry Medium 25922199
2016 Ubiquitinated Fancd2 recruits Fan1 to stalled replication forks; this recruitment is dispensable for ICL repair but is essential for restraining DNA replication fork progression and preventing chromosome abnormalities at stalled forks. Fan1 nuclease-defective knockin mice are cancer-prone, and a Fan1 variant in pancreatic cancers abolishing Ub-Fancd2 recruitment causes genetic instability without affecting ICL repair. Fan1 nuclease-dead knockin mice, genetic epistasis, fork progression assay, cancer predisposition phenotype Science High 26797144
2016 The UBZ domain of FAN1 (needed for interaction with FANCD2) is not required for the initial rapid recruitment of FAN1 to ICLs or for cellular ICL resistance; epistasis analyses show FAN1 has ICL repair activity independent of Fanconi anemia proteins and redundant with 5'-3' exonuclease SNM1A. Fan1-deficient mouse, UBZ-mutant knockin, survival assay, epistasis (Fan1/Snm1a double knockout) Genes & development High 26980189
2016 Fan1 nuclease-defective (Fan1^nd/nd) mice develop karyomegalic interstitial nephritis; karyomegalic nuclei are polyploid and fibroblasts from these mice become polyploid upon ICL induction, demonstrating that FAN1 nuclease activity controls ploidy during ICL repair; this role is not shared by the Fanconi anemia pathway or SLX4-SLX1. Nuclease-dead knockin mice, ploidy analysis, genetic epistasis Genes & development High 26980188
2018 FAN1 binds to expanded HTT CAG repeat DNA directly; overexpression of FAN1 reduces CAG repeat expansion in cells expressing mutant HTT exon 1, and FAN1 nuclease activity is NOT required for this protection against CAG repeat expansion. DNA binding assay, repeat expansion assay in human cells and patient-derived stem cells/neurons, FAN1 overexpression/knockdown, nuclease-dead mutant Human molecular genetics Medium 30358836
2018 FAN1 protects against somatic CGG repeat expansion in a Fragile X mouse model; Fan1-/- mice show 2–3 times more somatic expansions in brain and other tissues but no effect on germ-line expansions. Fan1 knockout mouse model, repeat expansion analysis across tissues DNA repair Medium 29990673
2018 Bacterial FAN1 (PaFAN1) ortholog uses a conserved Arg/Lys patch to recognize phosphate groups near the 5' terminus; a basic pocket for initial endonuclease activity and this patch for subsequent exonuclease activity act complementarily in ICL unhooking; simultaneous disruption of both regions in human FAN1 significantly reduces ICL-resolving activity. Crystal structures of PaFAN1-DNA complexes, mutagenesis, in vitro ICL unhooking assay Journal of biological chemistry High 29514982
2012 FAN1 protein levels are regulated during the cell cycle; FAN1 is degraded during mitotic exit by the APC/C^Cdh1 ubiquitin ligase via KEN box and D-box degrons; overexpression or depletion of FAN1 affects progression through mitotic exit. Protein degradation assay, APC/C component co-expression, KEN-box/D-box mutagenesis Chinese journal of cancer Medium 22854063
2020 Fan1 knockout increases somatic expansion of Htt CAG repeats in knockin mice; simultaneous knockout of Mlh1 blocks Fan1 knockout-induced acceleration of somatic CAG expansion, indicating that MLH1 function is required for the CAG-destabilizing effect of FAN1 loss. Fan1 knockout mice, Mlh1 knockout epistasis, CAG repeat expansion analysis in tissues Human molecular genetics High 32876667
2020 FAN1 missense variants R507H and R377W (associated with HD onset hastening) reduce FAN1 DNA-binding activity and its capacity to rescue mitomycin C-induced cytotoxicity; FAN1 knockout in HD-iPSCs increased CAG repeat expansion. DNA binding assay, MMC survival complementation, FAN1 KO in iPSCs with CAG expansion assay American journal of human genetics Medium 32589923
2020 FAN1 is recruited to chromatin through interaction with MLH1 (not FANCD2) following O6-methylguanine damage; FAN1 forms nuclear foci colocalizing with MLH1 and ssDNA; FAN1-knockdown cells show reduced ssDNA generation and MNU-induced apoptosis, suggesting FAN1 exonuclease activity at MLH1-directed sites produces ssDNA that triggers the DNA damage response and apoptosis. Co-immunoprecipitation, immunofluorescence/foci analysis, siRNA knockdown, sub-G1/caspase-9 apoptosis assay Genes to cells Medium 31955481
2021 FAN1 contains a conserved N-terminal SPYF motif that binds MLH1; this interaction is phospho-regulated—FAN1-S126 phosphorylation by cyclin-dependent kinases hinders FAN1-MLH1 association in a cell-cycle-dependent manner and is attenuated upon ICL induction; disrupting the FAN1-MLH1 interaction causes cellular hypersensitivity to ICL damage and defective repair of CAG/CTG slip-outs. Mutagenesis, Co-IP, phosphorylation assay, ICL survival assay, CAG/CTG slip-out repair assay Science advances High 34330701
2021 FAN1 has two distinct functions in CAG repeat stabilization: (1) it binds MLH1 via an N-terminal SPYF motif to restrict MLH1 recruitment by MSH3, thereby inhibiting assembly of a functional MMR complex that promotes expansion; (2) it promotes accurate repair via its nuclease activity. SPYF motif mutagenesis, Co-IP, MSH3 competition assay, MMR complex assembly assay, nuclease-dead mutant Cell reports High 34469738
2021 FAN1 exonuclease activity shows iterative pausing on CAG and CTG slip-out structures (at 5'-C↓A↓GC↓A↓G-3' and 5'-C↓T↓G↓C↓T↓G-3' sites); this pausing is slip-out-specific, and the ligand naphthyridine-azaquinolone requires FAN1 for its contraction-inducing effect in vivo. FAN1 endonucleolytic cleavage is insensitive to slip-outs. In vitro nuclease cleavage mapping on defined slipped-DNA substrates, FAN1 mutant analysis, cell-based expansion assay with ligand Cell reports Medium 34879276
2021 FAN1 nuclease activity is required for protection against CGG repeat expansion in a Fragile X mouse model (nuclease-domain point mutant phenocopies null); FAN1 and EXO1 have additive effects in protecting against MSH3-dependent expansions; FANCD2 loss has no effect on expansions, demonstrating FAN1's repeat-protective function is independent of the canonical FA pathway. Nuclease-domain knockin mouse model, FAN1/EXO1 double mutant analysis, FANCD2 knockout epistasis, repeat expansion measurement Nucleic acids research High 34718701
2022 FAN1 nuclease variants clustering in DNA-binding and nuclease domains are associated with earlier HD onset; purified FAN1 variant nuclease activities in vitro correlate with residual age at motor onset; mutating endogenous FAN1 to a nuclease-inactive form in iPSCs produces CAG expansion rates similar to complete FAN1 knockout. Exome sequencing of HD extremes, in vitro nuclease assay of purified variants, nuclease-dead knockin iPSC model with CAG expansion assay Nature neuroscience High 35379994
2023 FAN1 removes triplet repeat extrahelical extrusions via a PCNA- and RFC-dependent mechanism; RFC-PCNA confers strand directionality to FAN1 nuclease and requires physical interaction between PCNA and FAN1; this FAN1-PCNA-RFC-dependent extrusion removal competes with MutSβ-dependent MMR (which promotes longer-tract expansion) via a very short patch excision-repair mechanism. In vitro nuclease assay on defined extrusion substrates, PCNA/RFC activation assay, FAN1-PCNA interaction assay, cell extract-based CAG extrusion removal assay PNAS High 37549289
2024 miR-124-3p selectively targets the reference allele at rs3512 in the FAN1 3'-UTR, reducing FAN1 mRNA stability and protein levels; the alternative allele at rs3512 is less susceptible to miR-124-3p-mediated repression, resulting in increased FAN1 expression and delayed HD onset; validated by antagomir and 3'-UTR reporter assays with swapped alleles. 3'-UTR reporter assay with allele swap, antagomir treatment, allelic imbalance analysis PNAS Medium 38607933
2025 Cryo-EM structures of FAN1-PCNA-DNA ternary complex reveal that FAN1 R507 directly contacts PCNA D232; R507H mutation attenuates FAN1-PCNA complex assembly on CAG extrahelical extrusions and abolishes PCNA-FAN1-dependent cleavage of these extrusions; PCNA modulates FAN1 activity but does not affect FAN1's DNA binding affinity alone. Cryo-EM structure determination, biophysical binding assays, in vitro nuclease assay on CAG extrusion substrates, R507H and PCNA-interaction mutants Nature communications High 40368883 40368897
2025 FAN1, stimulated by RFC-PCNA, cleaves DNA at the 3' boundary of extrahelical loops and restricts its exonuclease activity; subsequent Polδ action removes the loop and resynthesizes DNA, causing repeat contraction; FAN1 also directly inhibits MutLγ, preventing its activation by MutSβ, thereby opposing the MutLγ-mediated expansion mechanism. Reconstituted in vitro assay with purified human proteins, nuclease activity mapping, MutLγ inhibition assay Nature communications High 41145416
2026 USP7 (ubiquitin-specific protease 7) interacts with FAN1 and stabilizes FAN1 protein levels by deubiquitination, preventing proteasomal degradation; USP7 depletion reduces FAN1 chromatin association, increases cellular sensitivity to ICL damage, and accelerates CAG repeat expansion. Co-IP (FAN1-USP7 interaction), protein stability assay with proteasome inhibitor, chromatin fractionation, ICL sensitivity assay, CAG expansion cell model Nature communications Medium 41786746
2022 In Fan1-deficient kidney proximal tubule cells, persistent DNA damage leads to overexpression of DNA replication factors CDT1 and CDC6, causing polyploidization through failure to complete mitosis; inhibiting DNA replication with Roscovitine reduces tubular injury and blocks KIN development. Fan1 knockout mouse, in vitro/in vivo CDT1/CDC6 expression analysis, pharmacological Roscovitine treatment with functional rescue Kidney international Medium 35931300

Source papers

Stage 0 corpus · 58 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 A genetic screen identifies FAN1, a Fanconi anemia-associated nuclease necessary for DNA interstrand crosslink repair. Molecular cell 283 20603073
2010 Identification of KIAA1018/FAN1, a DNA repair nuclease recruited to DNA damage by monoubiquitinated FANCD2. Cell 251 20603015
2010 Deficiency of FANCD2-associated nuclease KIAA1018/FAN1 sensitizes cells to interstrand crosslinking agents. Cell 221 20603016
2010 FAN1 acts with FANCI-FANCD2 to promote DNA interstrand cross-link repair. Science (New York, N.Y.) 209 20671156
2012 FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair. Nature genetics 188 22772369
2019 FAN1 modifies Huntington's disease progression by stabilizing the expanded HTT CAG repeat. Human molecular genetics 109 30358836
2016 Ubiquitinated Fancd2 recruits Fan1 to stalled replication forks to prevent genome instability. Science (New York, N.Y.) 105 26797144
2015 Germline Mutations in FAN1 Cause Hereditary Colorectal Cancer by Impairing DNA Repair. Gastroenterology 83 26052075
2010 KIAA1018/FAN1 nuclease protects cells against genomic instability induced by interstrand cross-linking agents. Proceedings of the National Academy of Sciences of the United States of America 77 21115814
2022 Exome sequencing of individuals with Huntington's disease implicates FAN1 nuclease activity in slowing CAG expansion and disease onset. Nature neuroscience 65 35379994
2020 Promotion of somatic CAG repeat expansion by Fan1 knock-out in Huntington's disease knock-in mice is blocked by Mlh1 knock-out. Human molecular genetics 65 32876667
2018 FAN1 protects against repeat expansions in a Fragile X mouse model. DNA repair 63 29990673
2013 Scan statistic-based analysis of exome sequencing data identifies FAN1 at 15q13.3 as a susceptibility gene for schizophrenia and autism. Proceedings of the National Academy of Sciences of the United States of America 63 24344280
2014 FANCD2-controlled chromatin access of the Fanconi-associated nuclease FAN1 is crucial for the recovery of stalled replication forks. Molecular and cellular biology 60 25135477
2014 DNA repair. Mechanism of DNA interstrand cross-link processing by repair nuclease FAN1. Science (New York, N.Y.) 59 25430771
2020 Genetic and Functional Analyses Point to FAN1 as the Source of Multiple Huntington Disease Modifier Effects. American journal of human genetics 57 32589923
2021 FAN1 controls mismatch repair complex assembly via MLH1 retention to stabilize CAG repeat expansion in Huntington's disease. Cell reports 56 34469738
2021 FAN1, a DNA Repair Nuclease, as a Modifier of Repeat Expansion Disorders. Journal of Huntington's disease 51 33579867
2016 Fan1 deficiency results in DNA interstrand cross-link repair defects, enhanced tissue karyomegaly, and organ dysfunction. Genes & development 48 26980189
2021 FAN1-MLH1 interaction affects repair of DNA interstrand cross-links and slipped-CAG/CTG repeats. Science advances 35 34330701
2016 Karyomegalic interstitial nephritis and DNA damage-induced polyploidy in Fan1 nuclease-defective knock-in mice. Genes & development 35 26980188
2014 Structural insights into 5' flap DNA unwinding and incision by the human FAN1 dimer. Nature communications 35 25500724
2022 Persistent DNA damage underlies tubular cell polyploidization and progression to chronic kidney disease in kidneys deficient in the DNA repair protein FAN1. Kidney international 33 35931300
2012 On the role of FAN1 in Fanconi anemia. Blood 30 22611161
2023 FAN1 removes triplet repeat extrusions via a PCNA- and RFC-dependent mechanism. Proceedings of the National Academy of Sciences of the United States of America 23 37549289
2021 FAN1 exo- not endo-nuclease pausing on disease-associated slipped-DNA repeats: A mechanism of repeat instability. Cell reports 23 34879276
2013 The conserved Fanconi anemia nuclease Fan1 and the SUMO E3 ligase Pli1 act in two novel Pso2-independent pathways of DNA interstrand crosslink repair in yeast. DNA repair 23 24192486
2014 FAN1 activity on asymmetric repair intermediates is mediated by an atypical monomeric virus-type replication-repair nuclease domain. Cell reports 21 24981866
2014 Crystal structure of a Fanconi anemia-associated nuclease homolog bound to 5' flap DNA: basis of interstrand cross-link repair by FAN1. Genes & development 21 25319828
2017 Structural and functional relationships of FAN1. DNA repair 20 28623094
2010 Human KIAA1018/FAN1 localizes to stalled replication forks via its ubiquitin-binding domain. Cell cycle (Georgetown, Tex.) 20 20935496
2021 FAN1's protection against CGG repeat expansion requires its nuclease activity and is FANCD2-independent. Nucleic acids research 17 34718701
2011 FAN1 variants identified in multiple-case early-onset breast cancer families via exome sequencing: no evidence for association with risk for breast cancer. Breast cancer research and treatment 13 21858661
2010 DNA repair has a new FAN1 club. Molecular cell 11 20670886
2024 Posttranscriptional regulation of FAN1 by miR-124-3p at rs3512 underlies onset-delaying genetic modification in Huntington's disease. Proceedings of the National Academy of Sciences of the United States of America 10 38607933
2020 Karyomegalic interstitial nephritis with a novel FAN1 gene mutation and concurrent ALECT2 amyloidosis. BMC nephrology 9 32111193
2020 MLH1-mediated recruitment of FAN1 to chromatin for the induction of apoptosis triggered by O6 -methylguanine. Genes to cells : devoted to molecular & cellular mechanisms 8 31955481
2015 Human FAN1 promotes strand incision in 5'-flapped DNA complexed with RPA. Journal of biochemistry 8 25922199
2023 Modeling of FAN1-Deficient Kidney Disease Using a Human Induced Pluripotent Stem Cell-Derived Kidney Organoid System. Cells 7 37759541
2021 New familial cases of karyomegalic interstitial nephritis with mutations in the FAN1 gene. BMC medical genomics 7 34126972
2012 Human KIAA1018/FAN1 nuclease is a new mitotic substrate of APC/C(Cdh1). Chinese journal of cancer 7 22854063
2023 Mitochondrial ROS Triggers KIN Pathogenesis in FAN1-Deficient Kidneys. Antioxidants (Basel, Switzerland) 6 37107275
2020 Common variants in FAN1, located in 15q13.3, confer risk for schizophrenia and bipolar disorder in Han Chinese. Progress in neuro-psychopharmacology & biological psychiatry 6 32450113
2018 Structural mechanism of DNA interstrand cross-link unhooking by the bacterial FAN1 nuclease. The Journal of biological chemistry 6 29514982
2020 Novel Homozygous FAN1 Mutation in a Familial Case of Karyomegalic Interstitial Nephritis. Indian journal of nephrology 5 33273795
2025 A FAN1 point mutation associated with accelerated Huntington's disease progression alters its PCNA-mediated assembly on DNA. Nature communications 4 40368883
2025 Structural and molecular basis of PCNA-activated FAN1 nuclease function in DNA repair. Nature communications 4 40368897
2024 Phenotypic and Genotypic Features of the FAN1 Mutation-Related Disease in a Large Hungarian Family. International journal of molecular sciences 4 38892095
2025 FAN1-mediated translesion synthesis and POLQ/HELQ-mediated end joining generate interstrand crosslink-induced mutations. Nature communications 3 40082407
2025 Mechanism of trinucleotide repeat expansion by MutSβ-MutLγ and contraction by FAN1. Nature communications 2 41145416
2024 Karyomegalic interstitial nephritis, a fascinating histopathologic entity for pathologists: Be watchful of the FAN1 gene mutations. Indian journal of pathology & microbiology 2 38847221
2024 Structural and molecular basis of FAN1 defects in promoting Huntington's disease. bioRxiv : the preprint server for biology 2 39416186
2024 A case of karyomegalic interstitial nephritis without FAN1 mutations in the setting of brentuximab, ifosfamide, and carboplatin exposure. BMC nephrology 2 39543462
2021 SPYing on triplet repeat expansions: Insights into FAN1-MLH1 interaction and regulation. Cell reports 2 34525375
2024 FAN1 Deletion Variant in Basenji Dogs with Fanconi Syndrome. Genes 1 39596669
2026 USP7 deubiquitinase stabilizes FAN1 to support DNA crosslink repair and suppress CAG repeat expansion. Nature communications 0 41786746
2026 Ruxolitinib-associated Karyomegalic Interstitial Nephritis Without FAN1 Mutation: Expanding the Etiology to JAK Inhibitors. Nephron 0 42139177
2024 A rare multisystemic disorder with chronic kidney disease: Karyomegalic interstitial nephritis due to homozygous FAN1 c.2260C>T variant. Nephrology (Carlton, Vic.) 0 39294548

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