Affinage

BRIP1

Fanconi anemia group J protein · UniProt Q9BX63

Length
1249 aa
Mass
140.9 kDa
Annotated
2026-06-09
100 papers in source corpus 40 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BRIP1 (BACH1/FANCJ) is a 5′-to-3′ DEAH-box ATP-dependent DNA helicase that maintains genome stability during DNA replication and repair, and its loss defines Fanconi anemia complementation group J (PMID:16153896, PMID:16116423, PMID:16116424, PMID:16116421). Catalytic activity depends on an N-terminal iron–sulfur cluster coordinated by three conserved cysteines—mutated in Fanconi anemia and cancer—and on Q-motif (Q25)-dependent dimerization, with the dimer showing enhanced ATPase, helicase, and DNA-binding activity (PMID:16973432, PMID:22582397, PMID:32542039). The enzyme unwinds duplex DNA, dissociates G-quadruplex (G4) structures, disrupts triplex DNA and protein–DNA complexes, and inhibits RAD51 strand exchange, contacting both translocating and non-translocating strands during unwinding (PMID:18426915, PMID:18978354, PMID:19150983, PMID:17145708). A central physiological role is resolving G4 obstacles during replication: FANCJ counteracts fork stalling at G4 structures—a function it performs in cell-free Xenopus extracts independently of the canonical FA pathway—and engages G4s through a dedicated AKKQ recognition motif that also mediates MLH1 binding, while a PIP-like region recruits REV1 to assemble a G4 repair complex (PMID:23530069, PMID:25193968, PMID:27342280, PMID:31861576). FANCJ operates in interstrand crosslink repair downstream of FANCD2 monoubiquitination, where its helicase activity and direct MLH1 (MutLα) interaction—rather than its BRCA1 interaction—are required to correct ICL sensitivity (PMID:16116421, PMID:17581638). FANCJ directly binds and stabilizes FANCD2/FANCI and is reciprocally required for FANCD2 chromatin loading and focus formation (PMID:25070891, PMID:26336824, PMID:20676667). In homologous recombination, CDK-dependent S990 phosphorylation drives both BRCA1 interaction and K1249 acetylation, the latter recruiting CtIP to promote DNA end resection (PMID:32251466, PMID:22792074). FANCJ couples to checkpoint and replication-stress responses via phospho-Thr1133-dependent binding to the TopBP1 BRCT7/8 domains, supporting ATR signaling and RPA chromatin loading, and cooperates with RPA on damaged and G4 substrates (PMID:20159562, PMID:21127055, PMID:17596542). Genetically, FANCJ helicase function suppresses spontaneous and replication-stress-induced microsatellite instability independently of FANCD2, with Fancj-null mice predisposed to lymphoma (PMID:26637282, PMID:27179029). Beyond replication and repair, FANCJ unfolds protein adducts in DNA–protein crosslink repair to enable SPRTN cleavage and translesion synthesis (PMID:36608669), and contributes to S-phase PARP1 activity through its MLH1 interaction, explaining its requirement for PARP inhibitor efficacy in BRCA1-deficient cells (PMID:38521768).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2005 High

    Established that the BRCA1-interacting helicase BACH1 is the FANCJ gene, connecting a DNA helicase to the Fanconi anemia crosslink-repair disorder.

    Evidence Nonsense mutation identification in FA-J patient cells with complementation rescue of MMC-induced G2/M arrest

    PMID:16116423 PMID:16116424 PMID:16153896

    Open questions at the time
    • Did not define the biochemical helicase substrate spectrum
    • Did not place FANCJ relative to FANCD2 activation in the pathway
  2. 2005 High

    Showed FANCJ acts downstream of FANCD2 monoubiquitination and independently of its BRCA1 interaction in the FA pathway.

    Evidence DT40 brip1 knockout with BRCT-interaction-domain deletion rescue and cisplatin sensitivity/cell-cycle analysis

    PMID:16116421

    Open questions at the time
    • Did not identify which alternative partner mediates the ICL function
    • Mechanism of FANCD2-FANCJ coordination unresolved
  3. 2006 High

    Identified the iron-sulfur cluster and Q-motif dimerization as structural determinants essential for catalysis, explaining how clinical mutations inactivate the enzyme.

    Evidence Cysteine and Q25 mutagenesis with in vitro helicase/ATPase assays, biophysical oligomerization analysis, and cellular complementation

    PMID:16973432 PMID:17145708 PMID:22582397

    Open questions at the time
    • No full-length structure of FANCJ
    • How dimerization is regulated in cells is unknown
  4. 2007 High

    Defined the MLH1 (MutLα) and RPA interactions as functional partners, with MLH1 binding (not BRCA1) required for ICL correction.

    Evidence Reciprocal Co-IP, domain mapping, complementation with interaction mutants, and RPA helicase-stimulation assays

    PMID:17581638 PMID:17596542

    Open questions at the time
    • RPA stimulation shown in a single lab
    • Structural basis of FANCJ-MLH1 binding not defined
  5. 2008 High

    Established G-quadruplex DNA as a physiological FANCJ substrate, unwound with 5′-to-3′ polarity and ATPase dependence, whose loss causes G4-associated genomic deletions.

    Evidence In vitro G4 helicase/ATPase assays with specificity controls plus genomic deletion analysis and telomestatin sensitivity in FA-J cells

    PMID:18426915 PMID:18978354

    Open questions at the time
    • Did not resolve how FANCJ recognizes G4 versus duplex
    • In vivo G4 sites not mapped
  6. 2009 High

    Broadened FANCJ's biochemical repertoire to triplex DNA, protein-DNA complex disruption, RAD51 inhibition, and a unique sensitivity to thymine glycol lesions.

    Evidence In vitro assays with purified recombinant FANCJ on triplex, protein-DNA, RAD51 strand-exchange, and oxidatively damaged substrates

    PMID:19150983 PMID:19419957

    Open questions at the time
    • Cellular relevance of triplex/protein-DNA activities not established at the time
    • Single-lab biochemistry
  7. 2010 High

    Connected FANCJ to replication-checkpoint control via phospho-Thr1133 recognition by TopBP1 BRCT7/8, with atomic-level structural mechanism, and to BRCA1-dependent repair pathway choice.

    Evidence Phospho-specific Co-IP, RPA/ATR functional assays, X-ray crystallography of the TopBP1-BACH1 phosphopeptide complex, and S990 phospho-mutant HR/Polη analysis

    PMID:20159562 PMID:20173781 PMID:20676667 PMID:21127055

    Open questions at the time
    • Kinase responsible for Thr1133 phosphorylation in vivo not pinned down
    • How checkpoint and ICL functions are temporally partitioned unclear
  8. 2012 Medium

    Linked FANCJ to epigenetic stability and transcriptional control near G4 motifs, and placed it downstream of FOXM1 in HR-based DSB repair.

    Evidence DT40 knockout epistasis with REV1/WRN/BLM, single-cell epigenetic readouts, ChIP/promoter analysis, and BRIP1 rescue of FOXM1 HR defect

    PMID:22021381 PMID:23108394

    Open questions at the time
    • Mechanism coupling G4 resolution to chromatin state not defined
    • Single-lab findings
  9. 2013 Medium

    Demonstrated that FANCJ resolves G4 obstacles in trans to sustain coordinated fork progression and prevent ssDNA gaps, with MLH1 (not BRCA1) directing damage-site localization.

    Evidence DNA fiber assays, leading/lagging-strand uncoupling analysis in FANCJ-null DT40 cells, and MLH1-interaction-mutant UV response assays

    PMID:23530069 PMID:24351291

    Open questions at the time
    • Single-lab models
    • How FANCJ selects sites for action during unperturbed replication unclear
  10. 2014 High

    Confirmed in a reconstituted replication system that FANCJ resolves G4-induced fork stalling independently of the FA pathway, and identified K1249 acetylation as a regulator of end processing.

    Evidence Xenopus egg extract replication with G4 templates and FANCJ immunodepletion; acetylation-site mutagenesis with RPA/RAD51 foci and checkpoint assays

    PMID:22792074 PMID:25193968

    Open questions at the time
    • Acetyltransferase/deacetylase enzymes not identified
    • Coupling between G4 stall resolution and downstream restart factors incomplete
  11. 2015 High

    Established FANCJ's helicase-independent stabilization of FANCD2/FANCI and its FA-independent suppression of microsatellite instability, with in vivo tumor predisposition.

    Evidence siRNA/inhibitor dissection and Co-IP for FANCD2 stabilization; Fancj knockout mice with MSI analysis, meiotic foci/chiasma counting, and comparison to Fancd2-null mice

    PMID:25070891 PMID:25659033 PMID:26336824 PMID:26490168 PMID:26637282

    Open questions at the time
    • Mechanism of helicase-independent FANCD2 stabilization unresolved
    • Basis of BLM compensation in meiosis not detailed
  12. 2016 High

    Defined a discrete AKKQ G4-recognition motif separate from the helicase core that overlaps the MLH1 interface, implying mutual exclusivity between G4 replication and ICL repair functions, and reaffirmed the Fe-S cluster requirement.

    Evidence Single-molecule FRET, ensemble helicase assays, AKKQ-mutant/MLH1 competition, and Fe-S mutant primer-extension/G4-ligand sensitivity assays

    PMID:27179029 PMID:27342280 PMID:32542039

    Open questions at the time
    • How the choice between G4 and MLH1-dependent functions is regulated in cells unknown
    • Structural model of AKKQ-G4 engagement incomplete
  13. 2018 Medium

    Showed FANCJ and the fork-remodeler HLTF counteract each other to balance fork remodeling and elongation.

    Evidence iPOND, DNA fiber assays, and S1-nuclease sensitivity in FANCJ/HLTF double-knockout cells

    PMID:30232006

    Open questions at the time
    • Direct physical interplay between FANCJ and HLTF not established
    • Single-lab study
  14. 2019 Medium

    Extended FANCJ function to transcriptional regulation, where lncRNA-tethered FANCJ unwinds promoter DNA, and detailed AKKQ/PIP-mediated G4 and REV1 engagement.

    Evidence RNA-DNA triplex/ChIP/reporter assays for REG3A and biolayer interferometry with FANCJ peptides, G4, REV1, and PCNA

    PMID:31767869 PMID:31861576

    Open questions at the time
    • Generality of the transcriptional role beyond REG3A unknown
    • Peptide-level binding not validated in full-length protein context
  15. 2020 Medium

    Defined a CDK-S990-phosphorylation → K1249-acetylation → CtIP-recruitment axis driving DNA end resection, with both scaffolding and helicase contributions.

    Evidence CtIP ChIP, FANCJ phospho/acetylation mutants, RPA/RAD51 foci, and ATPase-dead mutant analysis

    PMID:32251466

    Open questions at the time
    • Relative weight of scaffold versus catalytic contributions not quantified
    • Single-lab study
  16. 2023 High

    Identified a direct FANCJ role in DNA-protein crosslink repair, where it unfolds protein adducts to enable SPRTN cleavage and TLS.

    Evidence Xenopus egg extract DPC repair reconstitution with FANCJ immunodepletion, ATPase-dead mutants, and SPRTN cleavage/TLS assays

    PMID:36608669

    Open questions at the time
    • How FANCJ is recruited to DPC sites in cells unclear
    • Range of protein adducts unfolded not defined
  17. 2024 Medium

    Connected FANCJ to transcription-replication conflict resolution and S-phase PARP1 activity through MutSβ/MutLβ and MLH1-dependent mechanisms, explaining PARPi sensitivity in BRCA1-deficient cells.

    Evidence siRNA depletion, EdU replication-restart assays, MUS81 dependency, FANCJ helicase/MLH1 mutants, PARP activity assays, and PARPi sensitivity in BRCA1-deficient cells

    PMID:38324687 PMID:38521768

    Open questions at the time
    • Direct FANCJ-MutSβ physical interaction not structurally defined
    • Single-lab functional readouts

Open questions

Synthesis pass · forward-looking unresolved questions
  • How FANCJ's many context-specific functions—ICL repair, G4 resolution, end resection, DPC repair, checkpoint signaling, and transcriptional regulation—are partitioned and prioritized within a single cell cycle remains unresolved.
  • No integrated model of how post-translational modifications and partner switching select between mutually exclusive functions
  • No full-length structure to rationalize the multifunctional behavior
  • Regulation of dimer/monomer equilibrium in vivo unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 5 GO:0140657 ATP-dependent activity 4 GO:0003677 DNA binding 3 GO:0016787 hydrolase activity 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3
Pathway
R-HSA-69306 DNA Replication 4 R-HSA-73894 DNA Repair 4 R-HSA-8953897 Cellular responses to stimuli 3
Partners
BRCA1CTIPFANCD2FANCIMLH1REV1RPA1TOPBP1

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 BRIP1/BACH1 (FANCJ) is a DEAH-box DNA helicase that physically interacts with the BRCT domain of BRCA1 and is defective in Fanconi anemia complementation group J (FA-J); mutation of BACH1 in an FA-J patient-derived cell line was confirmed by western blot, and re-expression of wild-type BACH1 reduced the G2/M accumulation characteristic of FA cells after crosslinker treatment, establishing BACH1 as FANCJ. Homozygous nonsense mutation identification, western blot, complementation assay (MMC/G2-M rescue) Cancer cell High 16116423 16116424 16153896
2005 BRIP1 helicase function in the Fanconi anemia pathway is independent of its interaction with BRCA1: chicken DT40 brip1 knockout cells are proficient for FANCD2 ubiquitination but hypersensitive to cisplatin and arrested in late S-G2; expression of human BRIP1 lacking the BRCT-interaction domain rescued these defects, placing BRIP1 downstream of FANCD2 activation in the FA pathway. Homozygous knockout in DT40 cells, complementation with BRCT-interaction-domain deletion mutant, cisplatin sensitivity assay, cell-cycle analysis Nature genetics High 16116421
2006 FANCJ (and the related helicase XPD/Rad3) contain a conserved iron-sulfur (Fe-S) cluster domain near the N-terminus coordinated by three absolutely conserved cysteines; the Fe-S cluster is essential for helicase activity, and clinically relevant Fanconi anemia mutations in FANCJ disrupt this cluster and abolish helicase activity. Fe-S cluster characterization, mutagenesis of conserved cysteines, in vitro helicase assay, yeast repair assays Molecular cell High 16973432
2007 FANCJ physically interacts with the mismatch repair complex MutLα (MLH1/PMS2); FANCJ binds MLH1 directly through its helicase domain independently of BRCA1. Genetic studies showed that FANCJ helicase activity and MLH1 binding—but not BRCA1 binding—are essential to correct the ICL-induced 4N DNA accumulation and ICL sensitivity of FA-J cells. Co-immunoprecipitation, domain-mapping, complementation of FA-J cells with FANCJ interaction mutants, cell-cycle analysis after ICL treatment The EMBO journal High 17581638
2007 FANCJ co-immunoprecipitates with the RPA70 subunit of Replication Protein A (RPA); FANCJ colocalizes with RPA in nuclear foci after DNA damage in a BRCA1-dependent manner; RPA stimulates FANCJ helicase activity on duplex DNA substrates. Co-immunoprecipitation, immunofluorescence colocalization, in vitro helicase stimulation assay Blood Medium 17596542
2008 FANCJ unwinds G-quadruplex (G4) DNA substrates in an ATPase-dependent manner with 5′-to-3′ polarity; this activity is specific (RECQ1 failed to unwind all G4 substrates tested); RPA stimulates FANCJ G4 unwinding while MSH2/MSH6 inhibits it; FANCJ-depleted cells treated with the G4-interactive compound telomestatin show impaired proliferation, elevated apoptosis, and increased DNA damage, implicating G4 DNA as a physiological substrate. In vitro helicase assay on G4 substrates, ATPase assay, siRNA depletion, cell viability/apoptosis assays, γH2AX measurement Molecular and cellular biology High 18426915
2008 FANCJ is a structure-specific DNA helicase that dissociates G4 DNA with 5′-to-3′ polarity in vitro; loss of FANCJ G4 unwinding in the FA-J cell line EUFA0030 correlates with accumulation of large genomic deletions near G4 DNA signature sequences, supporting G4 resolution as a physiological function. In vitro G4 helicase assay with polarity determination, genomic deletion analysis in patient-derived FA-J cells The Journal of biological chemistry High 18978354
2009 FANCJ uses its motor ATPase to: (1) destabilize protein-DNA complexes, (2) unwind triplex (triple helix) DNA structures, and (3) inhibit RAD51 strand exchange in vitro, suggesting roles in controlling homologous recombination and resolving DNA structural obstacles. In vitro ATPase and helicase assays with purified recombinant FANCJ, protein-DNA complex disruption assay, RAD51 strand exchange inhibition assay The Journal of biological chemistry High 19150983
2009 FANCJ helicase is uniquely inhibited by a single thymine glycol lesion in either strand of a duplex substrate (unlike other helicases tested which show strand-specific inhibition); RPA (but not E. coli SSB) relieves FANCJ inhibition when the lesion is in the non-translocating strand, suggesting a strand-specific functional interaction between RPA and FANCJ on damaged DNA. In vitro helicase assay on defined oxidatively damaged substrates, comparison with BLM/RECQ1/WRN/DinG/DnaB/UvrD, RPA stimulation assay The Journal of biological chemistry High 19419957
2010 FANCJ/BACH1 interacts with TopBP1 through S-phase-specific phosphorylation of BACH1 at Thr1133, which is recognized by the C-terminal tandem BRCT7/8 domains of TopBP1. Both TopBP1 and BACH1 are required for ATR-dependent phosphorylation events and for RPA loading onto chromatin following replication stress, placing BACH1 early in replication checkpoint control. Co-immunoprecipitation, phospho-specific interaction mapping, RPA chromatin loading assay, ATR substrate phosphorylation assay after TopBP1/BACH1 depletion Molecular cell High 20159562
2010 Crystal structure of TopBP1 BRCT7/8 domains free and in complex with a phospho-Thr1133 BACH1/FANCJ peptide reveals a dramatic conformational change upon binding: the two BRCT repeats pivot about the BRCT-BRCT interface to form an extensive peptide-binding cleft; Thr(P) recognition mechanism is distinct from canonical BRCT-phosphopeptide interactions. Systematic mutagenesis confirmed key contact residues. X-ray crystallography, structure determination, site-directed mutagenesis The Journal of biological chemistry High 21127055
2010 FANCJ binding to BRCA1 (dependent on FANCJ phosphorylation at Ser990) regulates DNA repair pathway choice: a FANCJ mutant unable to bind BRCA1 inhibits homologous recombination and promotes Polη-dependent bypass; this bypass is dependent on FANCJ's direct interaction with MLH1. Phospho-mutant expression, HR reporter assay, Polη pathway analysis, MLH1 interaction-deficient mutants Oncogene Medium 20173781
2011 FANCJ coordinates two independent mechanisms to maintain epigenetic stability near G4 DNA motifs: one dependent on REV1 translesion polymerase and one dependent on WRN and BLM helicases. Loss of FANCJ leads to G4 motif-associated epigenetic instability (loss of transcriptional states) measurable at the single-cell level. DT40 cell genetic knockouts, cell-surface marker expression assay for epigenetic instability, transcriptional profiling, epistasis analysis Nucleic acids research Medium 22021381
2011 Oncogenic RAS downregulates BRIP1 expression, causing BRCA1 dissociation from chromatin and accumulation of DNA damage as part of RAS-induced senescence. Ectopic BRIP1 rescues BRCA1 chromatin association and suppresses RAS-induced senescence and DNA damage response, identifying BRIP1 as a physiological partner required for BRCA1 chromatin retention. Oncogenic RAS expression, chromatin fractionation, BRIP1 knockdown and overexpression, senescence assays, DNA damage marker analysis Developmental cell Medium 22137763
2012 FANCJ is acetylated at lysine 1249; acetylation at K1249 facilitates DNA end processing required for repair and checkpoint signaling (RPA foci formation, RPA phosphorylation, and RAD51 foci formation in response to camptothecin). Both preventing and mimicking FANCJ acetylation disrupts checkpoint maintenance; FANCJ acetylation is dispensable for ICL survival but shifts the mechanism toward recombination-dependent repair. Acetylation-site mutagenesis, RPA/RAD51 foci immunofluorescence, checkpoint assays, ICL survival assays PLoS genetics Medium 22792074
2012 FOXM1 transcription factor directly binds the BRIP1 promoter and drives BRIP1 expression; depletion of FOXM1 downregulates BRIP1 at mRNA and protein levels; FOXM1's requirement for homologous recombination-based DSB repair can be circumvented by reintroduction of BRIP1, placing BRIP1 downstream of FOXM1 in DSB repair. Promoter analysis, chromatin immunoprecipitation (ChIP) assay, siRNA knockdown, HR reporter assay (direct-repeat GFP), BRIP1 rescue experiment Oncogene Medium 23108394
2013 FANCJ promotes DNA replication in trans by counteracting fork stalling at G4 quadruplex structures; in ΔFANCJ cells, G4 stabilization restricts fork movement, uncouples leading- and lagging-strand synthesis, and generates single-stranded DNA gaps behind the fork. FANCJ also suppresses heterochromatin spreading by coupling fork movement through replication barriers with maintenance of chromatin structure. DNA fiber assay (fork velocity measurement), leading/lagging strand synthesis uncoupling assay, G4-stabilizing drug treatment, chromatin accessibility assays in FANCJ-null DT40 cells The Journal of cell biology Medium 23530069
2013 FANCJ localization to UV-induced damage sites requires its direct interaction with the MMR protein MLH1 (not BRCA1); FANCJ, its MLH1 interaction, and MSH2 function in a common pathway in response to UV irradiation to promote RPA phosphorylation and arrest of DNA synthesis; FANCJ-deficient cells show elevated mutation frequency after UV despite no increased UV killing. FANCJ interaction-mutant expression, RPA phosphorylation assay, DNA synthesis arrest measurement, mutation frequency assay after UV, epistasis with MSH2 Cancer research Medium 24351291
2014 Depletion of FANCJ helicase from Xenopus egg extracts causes persistent replication stalling at G-quadruplex structures; nascent strand synthesis stalls 1–2 nucleotides from the G4, and after transient stalling G4s are normally resolved. FANCJ performs this G4 replication function independently of the classical Fanconi anemia pathway. Xenopus egg extract replication system, ssDNA G4 template, FANCJ immunodepletion, nascent strand analysis The EMBO journal High 25193968
2014 FANCD2 and FANCJ directly interact in vitro and in vivo (reciprocal co-IP, gel filtration, and baculoviral co-expression); non-ubiquitinated FANCD2 (K561R mutant) constitutively interacts with FANCJ and impedes proper FANCJ chromatin localization; FANCJ is necessary for efficient FANCD2 chromatin loading and focus formation after mitomycin C, showing mutual regulation. Reciprocal co-immunoprecipitation, gel filtration, baculoviral protein expression, chromatin fractionation, immunofluorescence foci assay The Journal of biological chemistry High 25070891
2015 FANCJ-deficient mice (Fancj GT/GT) show increased MLH1 focus frequency during meiotic prophase I and increased chiasmata, indicating increased crossovers; this increase in crossovers correlates with increased BLM helicase localization, suggesting BLM compensates for FANCJ loss to facilitate crossing over. FANCJ interacts with MLH1 and BRCA1 in the meiotic context. Gene-trap mouse model, meiotic spread immunostaining for MLH1 and BLM foci, chiasma counting at diakinesis Chromosoma Medium 26490168
2015 Fancj helicase-deficient mice exhibit high levels of spontaneous microsatellite instability (MSI) that is exacerbated by replication inhibitors; MSI is not observed in Fancd2-deficient mice, demonstrating that FANCJ's role in MSI suppression is functionally distinct from its role in the canonical FA ubiquitination pathway. Fancj-null mice are also predisposed to lymphoma. Fancj knockout mice, microsatellite instability analysis, comparison with Fancd2-/- mice, replication inhibitor treatment, tumor surveillance Genes & development High 26637282
2015 FANCJ promotes stabilization of FANCD2 and FANCI proteins: depletion of FANCJ causes proteasome- and caspase-3-dependent degradation of FANCD2 and FANCI. FANCJ can complex with and stabilize FANCD2 even without a functional helicase domain, indicating this stabilization function is independent of helicase catalytic activity. siRNA depletion, proteasome inhibitor rescue, caspase-3 inhibitor rescue, co-immunoprecipitation with helicase-dead FANCJ mutant Oncotarget Medium 26336824
2015 FANCD2, FANCJ, and BRCA2 cooperate to promote replication fork restart after aphidicolin stalling independently of FA core complex-mediated monoubiquitination; non-ubiquitinated FANCD2 is sufficient for fork recovery together with FANCJ and BRCA2, supporting a non-linear FA pathway model at stalled forks. DNA fiber assay (fork restart), FA core complex mutant cell lines, FANCJ/BRCA2 depletion, monoubiquitination-deficient FANCD2 analysis Cell cycle Medium 25659033
2016 Single-molecule and ensemble biochemical analysis reveals FANCJ possesses a G4-specific recognition site (AKKQ motif) distinct from its helicase core; through this site FANCJ undergoes repeated rounds of stepwise G4-unfolding and refolding, partially stabilizing the G-quadruplex. The G4-recognition residues also participate in MLH1 interaction, suggesting FANCJ activity in G4 replication and ICL repair are mutually exclusive. Single-molecule FRET, ensemble helicase assays, FANCJ-AKKQ mutant analysis, MLH1 binding competition experiments Nucleic acids research High 27342280
2016 The Fe-S cluster of FANCJ is indispensable for DNA unwinding in vitro and for cellular resistance to ICL-inducing agents; cancer-associated FeS domain mutations abolish helicase activity and impair G4 unfolding on DNA templates in a primer extension assay with polymerase delta. FeS-cluster-deficient FANCJ variants retain partial ability to suppress replisome-associated G4 structures but sensitize cells to G4-stabilizing agents. In vitro helicase assay, ICL sensitivity assay, primer extension assay, G4-ligand sensitivity assay, replisome-G4 foci analysis PLoS genetics Medium 32542039
2016 FANCJ is essential for maintaining microsatellite structure genome-wide during replication stress: hydroxyurea or aphidicolin treatment of FANCJ-depleted cells causes loss of diverse microsatellite PCR signals and chromosome recombination at ectopic hairpin-forming CTG/CAG repeats; this phenotype is specific to FANCJ and is distinct from the intact FA pathway. FANCJ siRNA depletion, FANCJ-null patient cells, microsatellite PCR assay, DNA fiber analysis, chromosome recombination assay Nucleic acids research Medium 27179029
2017 FANCJ controls the balance between short-tract and long-tract gene conversions (STGC and LTGC) at chromosomal DSBs; FANCJ-deficient cells show reduced overall gene conversions biased toward LTGC. This regulation requires the FANCJ-BRCA1 interaction, and helicase activity is essential for controlling overall HR and terminating extended repair synthesis during sister chromatid recombination. I-SceI-induced chromosomal DSB, HR reporter assay, LTGC/STGC quantification, FANCJ interaction and helicase mutants Nucleic acids research Medium 28911102
2018 FANCJ knockout cells show aberrant accumulation of the fork remodeling factor HLTF at replication forks; HLTF contributes to fork degradation in FANCJ-KO cells. FANCJ-dependent unrestrained DNA synthesis in HLTF-deficient cells correlates with S1-nuclease sensitivity and fork degradation, indicating FANCJ and HLTF counteract each other to maintain fork remodeling/elongation balance. iPOND (isolation of proteins on nascent DNA), DNA fiber assay, FANCJ/HLTF double knockout analysis, S1-nuclease sensitivity assay Cell reports Medium 30232006
2020 FANCJ promotes DNA end resection by recruiting CtIP to DSB sites; this recruitment depends on FANCJ K1249 acetylation, which in turn requires CDK-mediated phosphorylation of FANCJ at S990. CDK phosphorylation of FANCJ at S990 also independently facilitates BRCA1 interaction at damage sites. ATP-hydrolysis-deficient FANCJ partially supports end resection, indicating both scaffolding and helicase activity contribute. CtIP ChIP assay, FANCJ phospho/acetylation mutants, RPA and RAD51 foci immunofluorescence, helicase-dead and ATPase-dead mutant analysis PLoS genetics Medium 32251466
2019 FANCJ is tethered to the core promoter of REG3A via an RNA-DNA triplex formed by lncRNA REG1CP; once at the promoter, FANCJ unwinds double-stranded DNA to facilitate a permissive state for glucocorticoid receptor α (GRα)-mediated REG3A transcription, identifying a transcriptional regulatory role for FANCJ. RNA-DNA triplex assay, ChIP, FANCJ chromatin recruitment, reporter assay for REG3A transcription, GRα binding assay Nature communications Medium 31767869
2019 FANCJ AKKQ peptide binds tightly to a TTA loop of G4 structures and is sequestered away from 8-oxoguanine damage in the G4; a FANCJ PIP-like region recruits REV1 polymerase preferentially over PCNA, suggesting FANCJ assembles a G4 repair complex by engaging both G4 recognition (via AKKQ) and REV1 recruitment (via PIP). Fluorescence spectroscopy, biolayer interferometry (BLI) with FANCJ peptides and G4/REV1/PCNA Genes Medium 31861576
2023 FANCJ helicase plays a direct role in DNA-protein crosslink (DPC) repair: FANCJ binds ssDNA downstream of a DPC and uses its ATPase activity to unfold the protein adduct, exposing the underlying DNA for SPRTN protease cleavage. FANCJ is also essential for SPRTN activation after CMG bypass of a DPC, and FANCJ-dependent DPC unfolding enables translesion DNA synthesis past DPCs that cannot be degraded by SPRTN. In vitro DPC repair reconstitution with Xenopus egg extracts, FANCJ immunodepletion, ATPase-dead mutant analysis, SPRTN cleavage assay, TLS assay past DPC Molecular cell High 36608669
2024 MutSβ, an MLH1-PMS1 heterodimer (MutLβ), and FANCJ are required for MUS81-initiated restart of DNA replication stalled at transcription-replication conflict (TRC)-associated G4/R-loops; MutSβ recruits FANCJ to G4s via its G4-binding activity, and the process depends on FANCJ helicase activity and FANCJ-MLH1 interaction. siRNA depletion of pathway components, DNA replication restart assay (EdU incorporation after G4/R-loop induction), FANCJ helicase and MLH1-interaction mutants, MUS81 dependency assay Science advances Medium 38324687
2024 FANCJ promotes PARP1 activity during S-phase DNA replication; in FANCJ-deficient cells, G-quadruplex structures sequester PARP1 and MSH2, reducing PARP1 activity. Loss of the FANCJ-MLH1 interaction also diminishes PARP1 activity. In BRCA1-deficient cells, FANCJ loss mirrors PARP1 loss in reducing S-phase PARP1 activity, explaining FANCJ's requirement for PARP inhibitor effectiveness in BRCA1-deficient contexts. PARP activity assay, G4 stabilization experiments, FANCJ-MLH1 interaction mutant, MSH2 depletion, BRCA1-deficient cell analysis, PARPi sensitivity assay Nature communications Medium 38521768
2006 BACH1 helicase requires contacts with both the translocating and non-translocating strands for efficient DNA unwinding; an increased motor ATPase variant (M299I) enables BACH1 to overcome backbone discontinuities, and increasing the 5′ tail length of the substrate allows loading and unwinding of backbone-modified substrates. In vitro helicase assay with backbone-modified substrates, ATPase measurement, M299I mutant analysis Nucleic acids research Medium 17145708
2012 The Q motif of FANCJ (invariant Q25) is essential for dimerization: wild-type FANCJ exists as both monomer and dimer by size exclusion chromatography and sedimentation velocity; the dimeric form has higher specific ATPase and helicase activities and greater DNA binding. The Q25A mutation prevents dimerization, abolishes helicase and ATPase activity, impairs DNA binding, and fails to complement fancj-null cell sensitivity to cisplatin or telomestatin. Size exclusion chromatography, sedimentation velocity, in vitro ATPase and helicase assays, DNA binding, cisplatin/telomestatin complementation The Journal of biological chemistry High 22582397
2010 FANCJ nuclear foci assemble during S phase and are induced by various stresses; FANCJ helicase activity and BRCA1-binding capacity are both required for FANCJ nuclear focus formation; FANCJ and FANCD2 substantially co-localize in foci, and FANCJ promotes assembly of FANCD2 nuclear foci, linking FANCJ to FANCD2 chromatin recruitment. FANCJ mutant expression (helicase-dead, BRCA1-binding-deficient), immunofluorescence foci analysis, FANCD2 foci quantification Chromosoma Medium 20676667

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles. Nature genetics 544 17033622
2008 FANCJ helicase defective in Fanconia anemia and breast cancer unwinds G-quadruplex DNA to defend genomic stability. Molecular and cellular biology 356 18426915
2005 The DNA helicase BRIP1 is defective in Fanconi anemia complementation group J. Nature genetics 347 16116423
2015 Germline Mutations in the BRIP1, BARD1, PALB2, and NBN Genes in Women With Ovarian Cancer. Journal of the National Cancer Institute 330 26315354
2005 BACH1 is critical for homologous recombination and appears to be the Fanconi anemia gene product FANCJ. Cancer cell 317 16153896
2011 Mutations in BRIP1 confer high risk of ovarian cancer. Nature genetics 300 21964575
2005 The BRCA1-interacting helicase BRIP1 is deficient in Fanconi anemia. Nature genetics 293 16116424
2006 The DNA repair helicases XPD and FancJ have essential iron-sulfur domains. Molecular cell 277 16973432
2008 FANCJ is a structure-specific DNA helicase associated with the maintenance of genomic G/C tracts. The Journal of biological chemistry 209 18978354
2011 FANCJ coordinates two pathways that maintain epigenetic stability at G-quadruplex DNA. Nucleic acids research 178 22021381
2005 The BRIP1 helicase functions independently of BRCA1 in the Fanconi anemia pathway for DNA crosslink repair. Nature genetics 176 16116421
2008 Mutagenic capacity of endogenous G4 DNA underlies genome instability in FANCJ-defective C. elegans. Current biology : CB 175 18538569
2007 The FANCJ/MutLalpha interaction is required for correction of the cross-link response in FA-J cells. The EMBO journal 154 17581638
2018 Cost-effectiveness of Population-Based BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2 Mutation Testing in Unselected General Population Women. Journal of the National Cancer Institute 153 29361001
2010 BACH1/FANCJ acts with TopBP1 and participates early in DNA replication checkpoint control. Molecular cell 132 20159562
2014 FANCJ promotes DNA synthesis through G-quadruplex structures. The EMBO journal 122 25193968
2007 FANCJ (BACH1) helicase forms DNA damage inducible foci with replication protein A and interacts physically and functionally with the single-stranded DNA-binding protein. Blood 102 17596542
2009 FANCJ uses its motor ATPase to destabilize protein-DNA complexes, unwind triplexes, and inhibit RAD51 strand exchange. The Journal of biological chemistry 98 19150983
2011 Screening for BRCA1, BRCA2, CHEK2, PALB2, BRIP1, RAD50, and CDH1 mutations in high-risk Finnish BRCA1/2-founder mutation-negative breast and/or ovarian cancer individuals. Breast cancer research : BCR 95 21356067
2011 Hereditary breast cancer and the BRCA1-associated FANCJ/BACH1/BRIP1. Future oncology (London, England) 92 21345144
2016 No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing. Journal of medical genetics 90 26921362
2016 G-quadruplex recognition and remodeling by the FANCJ helicase. Nucleic acids research 88 27342280
2007 DOG-1 is the Caenorhabditis elegans BRIP1/FANCJ homologue and functions in interstrand cross-link repair. Molecular and cellular biology 87 18086896
2020 BRIP1, RAD51C, and RAD51D mutations are associated with high susceptibility to ovarian cancer: mutation prevalence and precise risk estimates based on a pooled analysis of ~30,000 cases. Journal of ovarian research 85 32359370
2012 The Forkhead Box M1 protein regulates BRIP1 expression and DNA damage repair in epirubicin treatment. Oncogene 85 23108394
2013 FANCJ couples replication past natural fork barriers with maintenance of chromatin structure. The Journal of cell biology 83 23530069
2018 BRIP1 loss-of-function mutations confer high risk for familial ovarian cancer, but not familial breast cancer. Breast cancer research : BCR 82 29368626
2009 Welcome the family of FANCJ-like helicases to the block of genome stability maintenance proteins. Cellular and molecular life sciences : CMLS 81 19099189
2011 Oncogenic RAS regulates BRIP1 expression to induce dissociation of BRCA1 from chromatin, inhibit DNA repair, and promote senescence. Developmental cell 76 22137763
2011 BRIP1, PALB2, and RAD51C mutation analysis reveals their relative importance as genetic susceptibility factors for breast cancer. Breast cancer research and treatment 75 21409391
2015 FANCD2, FANCJ and BRCA2 cooperate to promote replication fork recovery independently of the Fanconi Anemia core complex. Cell cycle (Georgetown, Tex.) 63 25659033
2018 Opposing Roles of FANCJ and HLTF Protect Forks and Restrain Replication during Stress. Cell reports 62 30232006
2008 Are the so-called low penetrance breast cancer genes, ATM, BRIP1, PALB2 and CHEK2, high risk for women with strong family histories? Breast cancer research : BCR 62 18557994
2014 Molecular and cellular functions of the FANCJ DNA helicase defective in cancer and in Fanconi anemia. Frontiers in genetics 59 25374583
2009 A recurrent truncating germline mutation in the BRIP1/FANCJ gene and susceptibility to prostate cancer. British journal of cancer 56 19127258
2019 LncRNA REG1CP promotes tumorigenesis through an enhancer complex to recruit FANCJ helicase for REG3A transcription. Nature communications 55 31767869
2010 Targeting the FANCJ-BRCA1 interaction promotes a switch from recombination to poleta-dependent bypass. Oncogene 53 20173781
2008 A novel breast cancer-associated BRIP1 (FANCJ/BACH1) germ-line mutation impairs protein stability and function. Clinical cancer research : an official journal of the American Association for Cancer Research 52 18628483
2015 FANCJ suppresses microsatellite instability and lymphomagenesis independent of the Fanconi anemia pathway. Genes & development 51 26637282
2007 Tagging single nucleotide polymorphisms in the BRIP1 gene and susceptibility to breast and ovarian cancer. PloS one 50 17342202
2011 Fanconi anemia and Bloom's syndrome crosstalk through FANCJ-BLM helicase interaction. Trends in genetics : TIG 48 22024395
2010 Molecular basis of BACH1/FANCJ recognition by TopBP1 in DNA replication checkpoint control. The Journal of biological chemistry 48 21127055
2009 FANCJ helicase uniquely senses oxidative base damage in either strand of duplex DNA and is stimulated by replication protein A to unwind the damaged DNA substrate in a strand-specific manner. The Journal of biological chemistry 47 19419957
2003 Mutational analysis of the BRCA1-interacting genes ZNF350/ZBRK1 and BRIP1/BACH1 among BRCA1 and BRCA2-negative probands from breast-ovarian cancer families and among early-onset breast cancer cases and reference individuals. Human mutation 46 12872252
2019 Rare BRIP1 Missense Alleles Confer Risk for Ovarian and Breast Cancer. Cancer research 42 31822495
2005 Mutation analysis of FANCD2, BRIP1/BACH1, LMO4 and SFN in familial breast cancer. Breast cancer research : BCR 41 16280053
2012 FANCJ/BACH1 acetylation at lysine 1249 regulates the DNA damage response. PLoS genetics 40 22792074
2023 The FANCJ helicase unfolds DNA-protein crosslinks to promote their repair. Molecular cell 38 36608669
2010 FANCJ: solving problems in DNA replication. DNA repair 35 20122882
2008 Expression of the BRCA1-interacting protein Brip1/BACH1/FANCJ is driven by E2F and correlates with human breast cancer malignancy. Oncogene 35 18345034
2006 Inhibition of BACH1 (FANCJ) helicase by backbone discontinuity is overcome by increased motor ATPase or length of loading strand. Nucleic acids research 35 17145708
2016 FANCJ is essential to maintain microsatellite structure genome-wide during replication stress. Nucleic acids research 34 27179029
2009 FANCJ helicase operates in the Fanconi Anemia DNA repair pathway and the response to replicational stress. Current molecular medicine 34 19519404
2015 FancJ (Brip1) loss-of-function allele results in spermatogonial cell depletion during embryogenesis and altered processing of crossover sites during meiotic prophase I in mice. Chromosoma 33 26490168
2012 The Q motif of Fanconi anemia group J protein (FANCJ) DNA helicase regulates its dimerization, DNA binding, and DNA repair function. The Journal of biological chemistry 33 22582397
2019 Helicases FANCJ, RTEL1 and BLM Act on Guanine Quadruplex DNA in Vivo. Genes 32 31683575
2008 Mutational analysis of the breast cancer susceptibility gene BRIP1 /BACH1/FANCJ in high-risk non-BRCA1/BRCA2 breast cancer families. Journal of human genetics 32 18414782
2008 Mutation analysis of BRIP1/BACH1 in BRCA1/BRCA2 negative Chinese women with early onset breast cancer or affected relatives. Breast cancer research and treatment 31 18483852
2009 Evaluation of variants in the CHEK2, BRIP1 and PALB2 genes in an Irish breast cancer cohort. Breast cancer research and treatment 30 19763819
2008 Genomic stability: FANCJ-dependent G4 DNA repair. Current biology : CB 28 18644339
2020 FANCJ helicase promotes DNA end resection by facilitating CtIP recruitment to DNA double-strand breaks. PLoS genetics 27 32251466
2013 FANCJ localization by mismatch repair is vital to maintain genomic integrity after UV irradiation. Cancer research 27 24351291
2012 Germline mutations in BRIP1 and PALB2 in Jewish high cancer risk families. Familial cancer 27 22692731
2007 BRIP1 (BACH1) variants and familial breast cancer risk: a case-control study. BMC cancer 26 17504528
2020 Cancer-associated mutations in the iron-sulfur domain of FANCJ affect G-quadruplex metabolism. PLoS genetics 25 32542039
2019 Clinical importance of FANCD2, BRIP1, BRCA1, BRCA2 and FANCF expression in ovarian carcinomas. Cancer biology & therapy 25 30822218
2009 FANCM-FAAP24 and FANCJ: FA proteins that metabolize DNA. Mutation research 25 19379763
2019 BRIP-1 germline mutation and its role in colon cancer: presentation of two case reports and review of literature. BMC medical genetics 24 31064327
2019 Assembly of a G-Quadruplex Repair Complex by the FANCJ DNA Helicase and the REV1 Polymerase. Genes 23 31861576
2016 BRIP1, a potential candidate gene in development of non-BRCA1/2 breast cancer. Frontiers in bioscience (Elite edition) 23 26709662
2010 Assessing the link between BACH1/FANCJ and MLH1 in DNA crosslink repair. Environmental and molecular mutagenesis 23 20658644
2010 FANCJ/BRIP1 recruitment and regulation of FANCD2 in DNA damage responses. Chromosoma 23 20676667
2008 Spectrum of mutational events in the absence of DOG-1/FANCJ in Caenorhabditis elegans. DNA repair 23 18708164
2010 An MLH1 mutation links BACH1/FANCJ to colon cancer, signaling, and insight toward directed therapy. Cancer prevention research (Philadelphia, Pa.) 22 20978114
2018 A minimal threshold of FANCJ helicase activity is required for its response to replication stress or double-strand break repair. Nucleic acids research 21 29788478
2010 Mutation analysis of BRIP1 in male breast cancer cases: a population-based study in Central Italy. Breast cancer research and treatment 21 21165771
2021 An emerging picture of FANCJ's role in G4 resolution to facilitate DNA replication. NAR cancer 20 34873585
2024 MutSβ-MutLβ-FANCJ axis mediates the restart of DNA replication after fork stalling at cotranscriptional G4/R-loops. Science advances 19 38324687
2017 BRIP1 overexpression is correlated with clinical features and survival outcome of luminal breast cancer subtypes. Endocrine connections 19 29138235
2016 Getting Ready for the Dance: FANCJ Irons Out DNA Wrinkles. Genes 19 27376332
2014 The Fanconi anemia proteins FANCD2 and FANCJ interact and regulate each other's chromatin localization. The Journal of biological chemistry 19 25070891
2014 BRCA1 and FancJ cooperatively promote interstrand crosslinker induced centrosome amplification through the activation of polo-like kinase 1. Cell cycle (Georgetown, Tex.) 19 25483079
2012 Decreased FANCJ caused by 5FU contributes to the increased sensitivity to oxaliplatin in gastric cancer cells. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 19 22968820
2021 Age of ovarian cancer diagnosis among BRIP1, RAD51C, and RAD51D mutation carriers identified through multi-gene panel testing. Journal of ovarian research 18 33926482
2024 FANCJ promotes PARP1 activity during DNA replication that is essential in BRCA1 deficient cells. Nature communications 17 38521768
2016 The role of germline alterations in the DNA damage response genes BRIP1 and BRCA2 in melanoma susceptibility. Genes, chromosomes & cancer 17 27074266
2013 BRIP1 variations analysis reveals their relative importance as genetic susceptibility factor for cervical cancer. Biochemical and biophysical research communications 17 23473757
2013 FancJ regulates interstrand crosslinker induced centrosome amplification through the activation of polo-like kinase 1. Biology open 17 24167712
2021 Comprehensive Mutational Analysis of the BRCA1-Associated DNA Helicase and Tumor-Suppressor FANCJ/BACH1/BRIP1. Molecular cancer research : MCR 16 33619228
2020 Landscape of BRIP1 molecular lesions in gastrointestinal cancers from published genomic studies. World journal of gastroenterology 16 32231423
2015 FANCJ protein is important for the stability of FANCD2/FANCI proteins and protects them from proteasome and caspase-3 dependent degradation. Oncotarget 16 26336824
2015 BRIP1 inhibits the tumorigenic properties of cervical cancer by regulating RhoA GTPase activity. Oncology letters 16 26870246
2013 First evidence for the contribution of the genetic variations of BRCA1-interacting protein 1 (BRIP1) to the genetic susceptibility of cervical cancer. Gene 16 23644138
2013 Loss of the BRCA1-interacting helicase BRIP1 results in abnormal mammary acinar morphogenesis. PloS one 16 24040146
2012 FANCJ expression predicts the response to 5-fluorouracil-based chemotherapy in MLH1-proficient colorectal cancer. Annals of surgical oncology 16 22526901
2017 FANCJ helicase controls the balance between short- and long-tract gene conversions between sister chromatids. Nucleic acids research 15 28911102
2015 hMSH5 Facilitates the Repair of Camptothecin-induced Double-strand Breaks through an Interaction with FANCJ. The Journal of biological chemistry 15 26055704
2011 FancJ/Brip1 helicase protects against genomic losses and gains in vertebrate cells. Genes to cells : devoted to molecular & cellular mechanisms 15 21605288
2022 A Novel Role for BRIP1/FANCJ in Neuronal Cells Health and in Resolving Oxidative Stress-Induced DNA Lesions. Journal of Alzheimer's disease : JAD 14 34776453
2012 Association between BRIP1 (BACH1) polymorphisms and breast cancer risk: a meta-analysis. Breast cancer research and treatment 14 23225146

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