Affinage

FANCD2

Fanconi anemia group D2 protein · UniProt Q9BXW9

Length
1451 aa
Mass
164.1 kDa
Annotated
2026-06-09
100 papers in source corpus 60 papers cited in narrative 60 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FANCD2 is the central effector of the Fanconi anemia (FA) DNA repair pathway, originally identified by positional cloning as the FA-D2 gene product whose reintroduction complements mitomycin C sensitivity in patient cells (PMID:11239453). Its activation is governed by a regulated cycle of post-translational modification: ATR/ATM kinases phosphorylate FANCD2 (T691, S717) and its partner FANCI, priming the complex (PMID:16943440, PMID:36050501), after which the FA core complex — minimally the FANCB-FANCL-FAAP100 module using UBE2T as E2 — monoubiquitinates FANCD2 on K561 during S phase and in response to DNA damage (PMID:12239151, PMID:24905007, PMID:31873223). This modification drives translocation from soluble nucleoplasm to chromatin, where FANCD2 forms damage-induced foci with BRCA1 and RAD51 (PMID:12239151, PMID:15454491). FANCD2 functions as an obligate heterodimer with its paralog FANCI, and DNA engagement by the ID2 complex is required for efficient monoubiquitination (PMID:17412408, PMID:22287633, PMID:24623813). Structural studies establish that the unmodified ID2 complex is recruited to DNA and that monoubiquitination triggers a conformational closure into a sliding clamp that encircles dsDNA, with ubiquitin acting as a molecular pin at the I-D interface; the clamp diffuses on duplex DNA and stalls at ssDNA-dsDNA junctions found at stalled replication forks (PMID:21764741, PMID:32066963, PMID:32510829, PMID:39085614). Activated FANCD2 coordinates interstitial crosslink repair by recruiting the XPF-ERCC1/SLX4 nucleases for unhooking incisions, FAN1 and CtIP for end processing and resection, and by stabilizing RAD51 filaments and mediating strand exchange while protecting DNA ends from DNA2, MRE11, and EXO1 nucleases (PMID:20603015, PMID:24726325, PMID:24794430, PMID:24794434, PMID:27694619, PMID:37526271). The cycle is reversed by USP1-UAF1, which deubiquitinates K561 in a DNA- and FANCI-contact-dependent manner requiring a FANCD2-specific sequence in the USP1 N-terminus (PMID:18082605, PMID:31253762, PMID:33795880). Beyond crosslink repair, FANCD2 — including its non-ubiquitinated form — restrains replication fork progression at common fragile sites and in BRCA1/2-deficient cells where its loss is synthetic lethal, suppresses R-loop accumulation by recruiting RNA-processing factors and collaborating with SRSF1 for mRNA export, activates TAp63 transcription to suppress skin carcinogenesis, and localizes to mitochondria where it supports homeostasis through ATAD3 and TUFM (PMID:23806336, PMID:26797144, PMID:27768874, PMID:27264184, PMID:28378742, PMID:30431240, PMID:38165804).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2001 High

    Establishing the gene's identity and function answered whether FA-D2 cellular phenotypes arise from a single defined protein acting in crosslink repair.

    Evidence Positional cloning and retroviral complementation of MMC sensitivity in FA-D2 cells

    PMID:11239453

    Open questions at the time
    • Molecular mechanism of crosslink repair not defined
    • No biochemical activity assigned
  2. 2002 High

    Discovery that FANCD2 is monoubiquitinated on K561 during S phase and after damage, colocalizing with BRCA1/RAD51, revealed the key activating modification linking the FA pathway to homologous recombination factors.

    Evidence Immunofluorescence colocalization, fractionation, K561R mutant complementation

    PMID:12239151

    Open questions at the time
    • Identity of the responsible E3 ligase unknown at this stage
    • Functional consequence of chromatin loading unresolved
  3. 2004 High

    Mapping the upstream signaling and the modification dependency clarified how DNA damage signals are transduced to FANCD2 activation.

    Evidence ATR/RPA1 knockdown and Seckel cells; ATR phosphorylation of T691/S717; chromatin translocation dependent on K561 monoubiquitination

    PMID:15314022 PMID:15454491 PMID:16943440

    Open questions at the time
    • How phosphorylation mechanistically promotes ubiquitination unresolved
    • Role of C-terminal D1428 beyond chromatin binding unclear
  4. 2003 High

    Ruling BRCA1/BARD1 out as the essential FANCD2 E3 ligase forced the search for the genuine catalytic machinery.

    Evidence In vitro reconstitution plus siRNA and DT40 RING-domain knockouts

    PMID:12887909

    Open questions at the time
    • True E3 ligase not yet identified
    • Mechanism of BRCA1 chromatin-targeting effect undefined
  5. 2007 High

    Identification of FANCI as a monoubiquitinated paralog forming the ID complex, and of FANCL as the PHD-domain E3 plus USP1 as the deubiquitinase, defined the core catalytic and substrate architecture of the pathway.

    Evidence Mass spectrometry, reciprocal Co-IP, DT40 FANCL and USP1 knockouts, chromatin fractionation, K563R knock-in

    PMID:17352736 PMID:17412408 PMID:18082605

    Open questions at the time
    • Structural basis of dual ubiquitin-locking unresolved
    • Why deubiquitination is required for repair not mechanistically explained
  6. 2009 High

    Demonstrating direct DNA binding by FANCI and preferential ID-complex recognition of branched substrates explained how the complex senses damaged replication forks.

    Evidence Purified protein DNA-binding assays, EM of ring-like FANCD2, MRN-dependent stability assays

    PMID:19561358 PMID:19609304

    Open questions at the time
    • Conformational logic of DNA recognition not yet structurally defined
    • MRN regulation of stability mechanistically unclear
  7. 2011 High

    The first ID-complex crystal structure positioned the modification sites at the I-D interface, implying that ubiquitination and phosphorylation regulate complex assembly and DNA recognition.

    Evidence X-ray crystallography of the ~300 kDa ID complex with DNA-binding assays

    PMID:21764741

    Open questions at the time
    • Conformation of the ubiquitinated state not captured
    • DNA-encircling mechanism inferred but not visualized
  8. 2012 High

    Showing that DNA strictly stimulates monoubiquitination within the ID2 complex via FANCI DNA binding, and that a FANCD2 CUE domain noncovalently binds FANCI-ubiquitin, established how activation is coupled to DNA engagement and stabilized on chromatin.

    Evidence In vitro reconstitution with purified components, DNA substrate panels, CUE-domain mutant complementation

    PMID:22287633 PMID:22855611

    Open questions at the time
    • Structural state of the DNA-loaded ubiquitinated complex still unknown
    • CUE-ubiquitin contact not structurally resolved
  9. 2010 High

    Identifying FAN1, CtIP, and XPF-ERCC1/SLX4 as ubiquitin-FANCD2-dependent effectors defined how the activated clamp executes nucleolytic crosslink processing and resection.

    Evidence Co-IP, in vitro nuclease assays, Xenopus ICL repair with immunodepletion, in vitro fragment binding, NHEJ/HR pathway-choice assays

    PMID:20603015 PMID:24726325 PMID:24794430 PMID:24794434

    Open questions at the time
    • Spatial coordination of multiple nucleases at the lesion unresolved
    • Order of incision versus resection events not fully defined
  10. 2014 High

    Native FA core complex reconstitution defined the minimal FANCB-FANCL-FAAP100 module as the monoubiquitination unit with FANCL embedding required for activity and site specificity.

    Evidence Native avian FA core complex purification, in vitro ubiquitination, genetic minimal-subunit dissection

    PMID:24905007

    Open questions at the time
    • Roles of other core subunits in residual activity undefined
    • Atomic basis of FANCL-driven specificity not yet shown
  11. 2016 High

    Cryo-EM of unmodified and ubiquitinated ID complexes revealed an autoinhibited homodimer versus a DNA-encircling closed clamp pinned by ubiquitin, resolving the structural basis of activation.

    Evidence Cryo-EM of chicken and human FANCD2-FANCI complexes with recruitment assays

    PMID:27405460 PMID:32066963

    Open questions at the time
    • How the clamp scans for fork structures not addressed
    • Dynamics of opening/closing transitions unresolved
  12. 2016 High

    Revealing replication-protective and fragile-site functions of FANCD2, including FAN1 recruitment at forks, R-loop suppression, RAD51 stabilization, and synthetic lethality in BRCA1/2-deficient cells, expanded its role beyond canonical ICL repair.

    Evidence DNA fiber assays, FAN1 knockin mice, ChIP-seq and R-loop manipulation, RAD51 filament and nuclease-protection assays, isogenic BRCA-deficient viability

    PMID:26797144 PMID:27264184 PMID:27694619 PMID:27768874

    Open questions at the time
    • Relative contributions of ubiquitinated vs non-ubiquitinated FANCD2 to fork protection not fully separated
    • Mechanism of fragile-site stabilization incomplete
  13. 2013 High

    Linking monoubiquitinated FANCD2 to TAp63 transcriptional activation and tumor suppression connected the pathway to senescence and cancer control beyond direct repair.

    Evidence Fancd2-/- and Usp1-/- mouse models, ChIP, transcription assays, skin tumor challenge

    PMID:23806336

    Open questions at the time
    • Direct DNA-binding vs cofactor role in TAp63 activation unresolved
    • Generalizability beyond skin tumorigenesis untested
  14. 2019 High

    Defining the regulatory off-switch (CK2 phosphorylation) and the DNA/RNA/R-loop stimulation of ID2 ubiquitination clarified how the pathway is restrained and how it senses diverse nucleic acid structures.

    Evidence Phosphosite mapping, phosphomimetic FANCD2 ubiquitination and DNA-binding assays, in vitro RNA/R-loop binding and ubiquitination reconstitution

    PMID:30650351 PMID:31167143

    Open questions at the time
    • In vivo balance between CK2 inhibition and ATR activation undefined
    • Physiological RNA/R-loop substrate engagement in cells not directly proven
  15. 2020 High

    Structural and biochemical work on ATR phosphorylation of FANCI and the ubiquitin-induced 'Arm' interface explained how phosphorylation primes clamp closure and how ubiquitin protects the complex from premature deubiquitination.

    Evidence Cryo-EM of phosphomimetic and ubiquitinated ID2 complexes, biochemical ubiquitination/DNA binding with mutants

    PMID:32117957 PMID:32510829 PMID:36050501

    Open questions at the time
    • Kinetics of phosphorylation-to-ubiquitination handoff in cells unresolved
    • Coupling of clamp closure to downstream effector recruitment unclear
  16. 2021 High

    Structures of USP1-UAF1 bound to the ubiquitinated ID complex defined the substrate-recognition basis of FANCD2 deubiquitination, including the UAF1-FANCI interface and a FANCD2-specific USP1 N-terminal element.

    Evidence X-ray crystallography, cryo-EM of USP1-UAF1-monoUb-ID complex, mutagenesis and in vitro deubiquitination

    PMID:31253762 PMID:33795880

    Open questions at the time
    • How DNA dependence is structurally enforced not fully resolved
    • In vivo timing of deubiquitination relative to repair completion unclear
  17. 2024 High

    Single-molecule and cryo-EM analysis established FANCD2-FANCI as a sliding clamp that diffuses on dsDNA and stalls at ssDNA-dsDNA junctions, and a RAD51-mediator role for FANCD2, providing a unified surveillance and end-protection mechanism.

    Evidence DNA-tethered diffusion single-molecule imaging, cryo-EM of stalled vs sliding complexes, in vitro RAD51 filament and nuclease-inhibition assays

    PMID:37526271 PMID:39085614

    Open questions at the time
    • How sliding is initiated and terminated in chromatin context unresolved
    • Coupling of junction stalling to effector handoff incompletely defined
  18. 2024 Medium

    Identifying SRSF1 as an RNA-dependent FANCD2 partner linked monoubiquitination to mRNA export and R-loop suppression, integrating the FA pathway into RNA metabolism.

    Evidence Co-IP, RNA-dependent interaction and mRNA export assays, monoubiquitination assays, cancer mutant analysis

    PMID:38165804

    Open questions at the time
    • Single-lab characterization without orthogonal structural validation
    • Generality across transcript classes untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How FANCD2's multiple non-canonical roles (mitochondrial homeostasis, telomere/ALT regulation, transcriptional control) mechanistically relate to its core DNA-clamp activity remains unresolved.
  • Mitochondrial localization and ATP5α effects rest on single-lab Co-IP and ATP assays without reconstitution
  • Whether non-repair functions require clamp formation or are mechanistically distinct is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 7 GO:0060090 molecular adaptor activity 5 GO:0140096 catalytic activity, acting on a protein 3 GO:0003723 RNA binding 2 GO:0031386 protein tag activity 2 GO:0140110 transcription regulator activity 1
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 2 GO:0005654 nucleoplasm 1 GO:0005739 mitochondrion 1
Pathway
R-HSA-69306 DNA Replication 4 R-HSA-73894 DNA Repair 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-1640170 Cell Cycle 3
Partners
BRCA2CTIPFAN1FANCIFANCLRAD51UAF1USP1
Complex memberships
FANCI-FANCD2 (ID2) complex

Evidence

Reading pass · 60 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 FANCD2 encodes a novel 1451 amino acid nuclear protein with two isoforms; retroviral transduction of FANCD2 cDNA into FA-D2 cells complemented MMC sensitivity, establishing it as the FA-D2 gene product functioning in DNA crosslink repair. Positional cloning, retroviral complementation assay Molecular cell High 11239453
2002 FANCD2 undergoes monoubiquitination on K561 during S phase and in response to DNA damage; monoubiquitinated FANCD2 colocalizes with BRCA1 and RAD51 in S-phase nuclear foci, and this monoubiquitination is required for normal cell-cycle progression after MMC treatment. Immunofluorescence colocalization, cell fractionation, mutant complementation (K561R) Blood High 12239151
2002 FANCD2 and NBS1 colocalize in subnuclear foci after MMC treatment; ionizing radiation activates ATM- and NBS1-dependent phosphorylation of FANCD2, establishing an S-phase checkpoint function, and NBS1 cells are hypersensitive to MMC. Immunofluorescence colocalization, co-immunoprecipitation, phosphorylation assay Nature cell biology High 12447395
2003 BRCA1/BARD1 complex can reconstitute FANCD2 monoubiquitination in vitro, but siRNA knockdown of BRCA1 or ablation of BRCA1/BARD1 RING finger domains in DT40 cells does not impair FANCD2 ubiquitination; BRCA1 affects chromatin targeting of FANCD2 but is not the essential E3 ligase for FANCD2 monoubiquitination. In vitro ubiquitination reconstitution with purified proteins, siRNA knockdown, DT40 RING-domain knockout Molecular cell High 12887909
2003 Menin (MEN1 product) specifically interacts with FANCD2, and this interaction is enhanced by gamma-irradiation; loss of menin in mouse embryonic fibroblasts increases sensitivity to DNA damage, placing menin in the FANCD2-dependent DNA repair pathway. Co-immunoprecipitation, cell viability assay in menin-null MEFs Cancer research Medium 12874027
2004 ATR kinase and RPA1 are required for efficient FANCD2 monoubiquitination; deficiency of ATR (Seckel syndrome cells or siRNA silencing) results in radial chromosomes after MMC treatment, mimicking FA chromosome instability. siRNA knockdown of ATR/RPA1, cell line analysis (Seckel syndrome), radial chromosome assay Genes & development High 15314022
2004 FANCD2 directly interacts with BRCA2 via a conserved C-terminal site also bound by FANCG/XRCC9; this interaction was confirmed by co-immunoprecipitation from human and hamster cell extracts. FANCD2 focus formation is independent of BRCA2. FANCD2 colocalizes with RAD51 after MMC or hydroxyurea treatment and very tightly with PCNA after hydroxyurea. Yeast two-hybrid, co-immunoprecipitation, immunofluorescence colocalization Human molecular genetics Medium 15115758
2004 Monoubiquitination of FANCD2 on K561 is required for its translocation from the soluble nuclear compartment to chromatin; the C-terminal residue D1428 (encoded by exon 44) is independently required for functional complementation of FA-D2 cells even when monoubiquitination and chromatin binding are intact. Stable transfection of mutant FANCD2 constructs in FA-D2 fibroblasts, chromatin fractionation, MMC sensitivity assay Blood High 15454491
2004 In Xenopus egg extracts, linear and branched double-stranded DNA (but not single-stranded or Y-shaped DNA) rapidly triggers FANCD2 monoubiquitination in an FA core complex-dependent but ATRIP-independent manner, and monoubiquitinated FANCD2 associates with these DNA structures. Xenopus egg extract cell-free system, DNA structure panel, immunodepletion Molecular and cellular biology High 17420278
2005 FANCD2-disrupted DT40 cells are defective in HR-mediated DSB repair and immunoglobulin gene conversion; they show increased sister chromatid exchange and intact Rad51 foci, indicating FANCD2 promotes a subpathway of HR that mediates gene conversion via a mechanism avoiding crossovers. Gene disruption in DT40 cells, HR reporter assay, immunoglobulin gene conversion assay, Rad51 foci Molecular and cellular biology High 15601828
2006 ATR phosphorylates FANCD2 on T691 and S717; these phosphorylations promote FANCD2 monoubiquitination and enhance cellular resistance to DNA crosslinking agents and intra-S-phase checkpoint establishment. ATM also phosphorylates these sites in response to IR. Phosphosite mapping, ATR/ATM knockdown/inhibition, phosphomutant complementation, MMC sensitivity assay Molecular and cellular biology High 16943440
2006 Drosophila FANCD2 and FANCL function in a linear pathway in which FANCL is necessary for FANCD2 monoubiquitination; FANCD2 mutants show defects in the IR-inducible S-phase checkpoint and elevated mutation rates after nitrogen mustard, establishing conservation of FA pathway function. RNAi knockdown in Drosophila, crosslinker sensitivity assay, S-phase checkpoint assay, mutation assay DNA repair Medium 16860002
2007 FANCI is a monoubiquitinated paralog of FANCD2 that forms the FANCI-FANCD2 (ID) complex; the two proteins associate and localize together to chromatin in response to DNA damage. Monoubiquitination of each protein is important for maintaining ubiquitin on the other (dual ubiquitin-locking mechanism), and FANCI mutation causes FA complementation group I. Mass spectrometry identification, co-immunoprecipitation, chromatin fractionation, ubiquitination assays Cell High 17412408
2007 USP1 ablation in DT40 cells results in constitutively chromatin-bound monoubiquitinated FANCD2 and DNA crosslinker sensitivity, demonstrating that FANCD2 deubiquitination (not just ubiquitination) is required for efficient DNA crosslink repair; persistent PCNA monoubiquitination has negligible impact on DNA repair. DT40 USP1 gene disruption, crosslinker sensitivity assay, chromatin fractionation Molecular cell High 18082605
2007 The FA core complex and UBE2T are independently recruited to chromatin; E3 ligase activity is regulated by DNA damage-induced chromatin localization of the complex, not by complex assembly; FANCD2 accesses chromatin independently of the FA core complex. Chromatin fractionation, complementation with assembly-defective vs. E3 ligase-defective mutants, UBE2T localization assays Molecular and cellular biology Medium 17938197
2007 FANCL interacts with FANCD2 via its PHD domain (yeast two-hybrid and Co-IP); FANCL is required for FANCD2 monoubiquitination and focus formation; FANCL and monoubiquitination of FANCD2 K563 are both required for HR repair of I-SceI-induced DSBs at equivalent quantitative levels. Yeast two-hybrid, co-immunoprecipitation, DT40 FANCL knockout, I-SceI HR assay, knock-in K563R Genes to cells High 17352736
2008 FANCG phosphorylation on serine 7 is required for co-precipitation of a BRCA2-FANCD2-FANCG-XRCC3 (D1-D2-G-X3) complex; direct BRCA2-FANCD2 interaction requires FANCG and its S7 phosphorylation; FANCG and XRCC3 are epistatic for sensitivity to DNA crosslinking agents in DT40 cells. Co-immunoprecipitation in human and hamster cells, phospho-mutant FANCG constructs, DT40 epistasis assay Oncogene Medium 18212739
2009 FANCI directly binds DNA and forms a stable complex with FANCD2 via FANCI's C-terminal region (aa 1001–1328); the FANCI-FANCD2 complex preferentially binds branched DNA structures compared to each protein alone, suggesting recognition of damaged replication forks. Purified recombinant proteins, in vitro DNA binding assays with various substrates, co-immunoprecipitation, truncation/mutation analysis The Journal of biological chemistry High 19561358
2009 Inhibition of MRE11, NBS1, or RAD50 destabilizes FANCD2; purified FANCD2 is a ring-like particle by EM that preferentially binds ssDNA; inhibition of MRE11 nuclease activity decreases FANCD2 foci, indicating MRN complex is a crucial regulator of FANCD2 stability and promotes FANCD2 binding to ssDNA at MRN-processed DSBs. Electron microscopy of purified FANCD2, in vitro DNA binding assay, MRE11 inhibitor (Mirin), siRNA knockdown of MRN components The EMBO journal Medium 19609304
2009 In Xenopus egg extracts, FANCM chromatin binding and DNA damage-induced phosphorylation are controlled in part by the downstream FA pathway protein FANCD2, as well as by ATR and ATM kinases. Xenopus egg extract immunodepletion and add-back experiments, chromatin binding assays The Journal of biological chemistry Medium 19633289
2010 Monoubiquitinated FANCD2 recruits FAN1 (KIAA1018) to sites of DNA damage; FAN1 is a nuclease with 5' flap endonuclease and 5' exonuclease activities mediated by a VRR_nuc domain; FAN1 depletion causes ICL hypersensitivity and genome instability. Co-immunoprecipitation, in vitro nuclease assay, siRNA depletion, ICL sensitivity assay Cell High 20603015
2011 Crystal structure of the ~300 kDa FANCI-FANCD2 (ID) complex at 3.4 Å reveals that monoubiquitination and regulatory phosphorylation sites map to the I-D interface, suggesting these modifications occur on monomeric proteins or an opened complex and may stabilize heterodimerization. Each protein has binding sites for both ssDNA and dsDNA, suggesting the ID complex recognizes DNA structures at replication fork-ICL encounters. X-ray crystallography (3.4 Å crystal structure of ID complex; 7.8 Å FANCI-DNA), in vitro DNA binding assays Science High 21764741
2011 RAD18 binds FANCD2 (RING domain-dependent) and is required for efficient monoubiquitylation and chromatin localization of both FANCD2 and FANCI; RAD18 knockout cells show delayed FANCD2 foci formation and ICL sensitivity. FANCD2 ubiquitylation is normal in PCNA ubiquitylation-resistant cells, indicating RAD18 acts independently of PCNA ubiquitylation. Co-immunoprecipitation, RAD18 knockout cell lines, chromatin fractionation, MMC sensitivity assay Blood Medium 21355096
2012 Various forms of DNA (ssDNA, dsDNA, branched DNA) robustly stimulate FANCD2 monoubiquitylation in vitro up to near-in-vivo levels; this DNA stimulation strictly requires FANCI and FANCI's DNA-binding activity, demonstrating that FANCD2 monoubiquitination occurs within the FANCI-FANCD2 complex and requires DNA engagement. In vitro ubiquitination reconstitution with purified components, DNA panel assay, FANCI DNA-binding mutant Nucleic acids research High 22287633
2012 FANCD2 contains a CUE ubiquitin-binding domain that mediates noncovalent ubiquitin binding in vitro; the CUE domain is required for interaction with FANCI, chromatin retention of monoubiquitinated FANCD2 and FANCI, and efficient ICL repair, suggesting FANCD2 CUE domain noncovalently binds the ubiquitin on FANCI to stabilize the complex on chromatin. In vitro ubiquitin binding assay, mutant complementation in FA-D2 cells, co-immunoprecipitation, ICL sensitivity assay Blood Medium 22855611
2013 FANCD2 directly interacts with MCM2-MCM7 replicative helicase; ATR signaling promotes transient association of endogenous FANCD2 with MCM2-7 independently of FANCD2 monoubiquitination; FANCD2 restrains DNA synthesis under nucleotide-limiting conditions and prevents ssDNA accumulation and senescence entry. Proteomic screen of replisome-associated factors (nascent DNA pull-down), co-immunoprecipitation, DNA fiber assay, siRNA depletion Molecular cell High 23993743
2013 Monoubiquitinated FANCD2 activates transcription of the tumor suppressor TAp63, promoting cellular senescence and blocking skin tumorigenesis; Usp1-deficient mice with elevated FANCD2-Ub are resistant to skin tumors while Fancd2-deficient mice are prone to Ras-driven skin carcinogenesis. Mouse genetic models (Fancd2-/- and Usp1-/- knockout), ChIP, transcription assay, tumor challenge Molecular cell High 23806336
2013 mTOR regulates FANCD2 expression via NF-κB; mTOR deficiency or inhibition increases NF-κB nuclear translocation, enhancing NF-κB binding to the FANCD2 promoter to suppress FANCD2 expression; exogenous FANCD2 rescues the DNA damage response defect in mTOR-inhibited cells. Genetic mTOR targeting in HSPCs, ChIP for NF-κB at FANCD2 promoter, FANCD2 reconstitution rescue experiment Leukemia Medium 23538752
2014 Biochemical reconstitution of FANCD2 monoubiquitination using purified native avian FA core complex demonstrates that FANCL must be embedded in the complex for maximal activity and site specificity; a minimal subcomplex of FANCB-FANCL-FAAP100 is sufficient as the monoubiquitination module; cells defective in other subunits retain residual activity. Biochemical purification of native FA core complex, in vitro ubiquitination reconstitution, genetic analysis of minimal subunit requirements Molecular cell High 24905007
2014 XPF-ERCC1 cooperates with SLX4/FANCP to perform the DNA unhooking incisions during replication-coupled ICL repair in Xenopus egg extracts; efficient recruitment of XPF-ERCC1 and SLX4 to the ICL depends on FANCD2 and its ubiquitylation. Xenopus egg extract ICL repair assay, immunodepletion, nuclease recruitment analysis Molecular cell High 24726325
2014 CtIP directly interacts with FANCD2; monoubiquitination of FANCD2 and CtIP residues 166-273 are both required for the FANCD2-CtIP interaction and MMC-induced CtIP foci; FANCD2 and CtIP cooperate to promote RPA2 hyperphosphorylation accompanying DNA end resection at ICL-induced DSBs. Co-immunoprecipitation, in vitro binding with purified fragments, siRNA depletion, RPA2 phosphorylation assay Cell reports High 24794430 24794434
2014 Monoubiquitinated FANCD2 tethers CtIP to damaged chromatin; CtIP mutants defective in FANCD2 binding fail to associate with damaged chromatin, leading to increased non-homologous end-joining and ICL hypersensitivity; CtIP depletion aggravates genomic instability in FANCD2-deficient cells. Co-immunoprecipitation, chromatin recruitment assays, NHEJ/HR pathway choice assays, siRNA depletion Cell reports High 24794430 24794434
2014 CtIP is recruited by FANCD2 to stalled replication forks on chromatin independently of FANCD2 monoubiquitination; CtIP cooperates with FANCD2 to promote fork restart and suppress new origin firing in a BRCA1-dependent manner. Co-immunoprecipitation, DNA fiber assay, chromatin fractionation, aphidicolin treatment Human molecular genetics Medium 24556218
2014 Regulation of FANCD2 and FANCI monoubiquitination by DNA: duplex or branched DNA strongly stimulates FANCD2 monoubiquitination in the ID2 complex, but unstructured ssDNA or chromatinized DNA is not effective; FANCI DNA-binding mutants compromise FANCD2 ubiquitination; FANCL interaction with the ID2 complex is indispensable for E3 ligase efficacy. In vitro ubiquitination reconstitution with purified human FANCD2 and FANCI, DNA substrate panel, FANCI DNA-binding mutants Nucleic acids research High 24623813
2015 UHRF1 acts upstream of FANCD2 in the FA pathway: UHRF1 directly binds ICLs in vitro and in vivo, is rapidly recruited to chromatin before FANCD2, and its knockdown drastically reduces FANCD2 foci formation, indicating UHRF1 senses ICLs and recruits FANCD2. Biochemical ICL binding assay, live-cell imaging, siRNA knockdown, FANCD2 foci quantification Cell reports Medium 25801034
2015 FANCD2 promotes replication fork restart and suppresses new origin firing independently of FA core complex-mediated monoubiquitination after aphidicolin treatment; FANCJ and BRCA2 share this replication fork recovery role with non-ubiquitinated FANCD2, independently of the FA core complex. DNA fiber assay, FA core complex-deficient cells, monoubiquitination-deficient (K561R) FANCD2, chromatin fractionation Cell cycle Medium 25659033
2016 FANCD2-FANCI (ID) complex adopts a closed conformation when FANCD2 is monoubiquitinated, forming a channel that encloses dsDNA; ubiquitin acts as a covalent molecular pin at the FANCD2-FANCI interface to trap the complex on DNA; unmodified FANCD2 forms a homodimer unable to bind DNA, suggesting an autoinhibitory mechanism. Cryo-EM structure determination of chicken FANCD2 and FANCI complexes Nature structural & molecular biology High 32066963
2016 The FANCD2-FANCI complex is recruited to stalled replication forks (as detected at ICLs) before monoubiquitination; cryo-EM structure of the human FANCD2-FANCI complex shows an inner cavity large enough for dsDNA and a Tower domain; disease-causing mutations in the Tower domain impair FA pathway activation. Cryo-EM structure of human FANCD2-FANCI complex, replication fork recruitment assays Nature communications High 27405460
2016 Ubiquitinated FANCD2 recruits FAN1 to stalled replication forks to restrain fork progression and prevent chromosome abnormalities, even in the absence of ICLs; FAN1 nuclease-defective knockin mice are cancer-prone; a cancer-associated FAN1 variant abolishing Ub-FANCD2 binding causes genetic instability without affecting ICL repair. FAN1 knockin mice, DNA fiber assay, FAN1-FANCD2 interaction assay, cancer genetics Science High 26797144
2016 FANCD2 acts as a trans-acting facilitator of common fragile site (CFS) replication; in FANCD2-deficient cells, replication forks stall within AT-rich CFS cores leading to dormant origin activation; FANCD2 deficiency is associated with DNA:RNA hybrid formation at CFS-FRA16D, and inhibition of DNA:RNA hybrids suppresses replication perturbation. DNA fiber assay, ChIP-seq, R-loop inhibition, origin firing assay, FANCD2-deficient cells Molecular cell High 27768874
2016 FANCD2 is required for fork protection and restart in BRCA1/2-deficient tumors; FANCD2 promotes Polθ recruitment at sites of damage and alt-EJ repair; loss of FANCD2 in BRCA1/2-deficient tumors results in synthetic lethality. DNA fiber assay, Polθ recruitment assay, alt-EJ assay, cell viability in isogenic BRCA1/2-deficient cells Cell reports High 27264184
2016 Monoubiquitinated FANCD2 antagonizes the BLM helicase to restrain telomere replication and recombination in ALT cells; FANCD2 depletion causes a hyper-ALT phenotype with increased extrachromosomal telomeric repeat DNAs suppressed by BLM but not RAD51 loss. siRNA depletion, telomere FISH, PML body analysis, BLM/RAD51 epistasis Human molecular genetics Medium 27427384
2016 FANCI-FANCD2 complex directly binds RAD51 and stabilizes the RAD51-DNA filament; this DNA end protection from FAN1 nucleolytic degradation requires FANCI's DNA-binding activity (not FANCD2's), and is abolished by the RAD51 mutant from FANCR patient cells. Purified protein binding assays, RAD51 filament stability assay, nuclease protection assay, FANCI DNA-binding mutants Nucleic acids research High 27694619
2017 FANCD2 binds HPV genomes preferentially over cellular chromosomes and is required for maintenance of HPV episomes in undifferentiated basal epithelial cells; HPV-dependent FANCD2 foci colocalize with ATM pathway components (γH2AX, BRCA1) but not p-SMC1. ChIP for FANCD2 on HPV genomes, immunofluorescence colocalization, FANCD2 siRNA depletion, episome maintenance assay mBio Medium 28196964
2017 FANCD2 interacts with the spliceosomal protein SF3B1 (U2 snRNP component); replication stress induces ATR-dependent release of SF3B1 from nuclear speckles in a FANCI-dependent manner; both FANCD2 and FANCI associate with SF3B1 on chromatin and prevent accumulation of postcatalytic intron lariats. Co-immunoprecipitation, proximity ligation assay, siRNA depletion, splicing assay The Journal of cell biology Medium 29030393
2017 FANCD2 localizes to mitochondria where it associates with nucleoid complex components ATAD3 and TUFM; ATAD3-TUFM complex is disrupted in Fancd2-/- and Fanca-/- mice; FANCD2 mitochondrial localization requires ATAD3, suggesting a role in mitochondrial homeostasis. Flag/HA knock-in mouse mass spectrometry interactome, subcellular fractionation, co-immunoprecipitation, confocal imaging Scientific reports Medium 28378742
2017 Monoubiquitinated FANCD2 (but not K561R mutant) interacts with ATP5α; monoubiquitination-dependent localization of ATP5α within mitochondria is required for normal mitochondrial ATP production; loss of monoubiquitinated FANCD2 causes mislocalization of ATP5α and reduced mitochondrial ATP output. Co-immunoprecipitation, mitochondrial ATP assay, subcellular fractionation, protein docking Scientific reports Low 28687786
2018 FANCD2 accumulates at the central regions of large transcribed genes (common fragile sites) during replication stress in an R-loop-dependent manner (as shown by ChIP-seq and PLA); however, FANCD2 monoubiquitination and RPA foci formation are still induced in R-loop-depleted cells, indicating R-loops are needed for FANCD2 retention at chromatin but not for upstream FA pathway activation. ChIP-seq, proximity ligation assay (PLA), R-loop depletion, low-dose aphidicolin treatment Nucleic acids research Medium 29394375
2018 FANCD2 interacts with RNA processing factors hnRNP U and DDX47 and recruits them to R-loop-containing chromatin; this reduces transcription-replication collisions and lowers R-loop levels, contributing to genome stability during mild replication stress. Co-immunoprecipitation, proximity ligation assay between PCNA and RNA Pol II, R-loop quantification, siRNA depletion The FEBS journal Medium 30431240
2019 Purified human FANCI-FANCD2 (ID2) complex binds ssRNA and R-loop substrates with high affinity (preferring G-rich sequences) via recognition of displaced ssDNA and ssRNA; RNA and R-loop substrates strongly stimulate ID2 monoubiquitination in vitro with activity corresponding to binding affinity. In vitro binding assays with purified ID2 complex and synthetic RNA/R-loop substrates, in vitro ubiquitination reconstitution Cell reports High 30650351
2019 Efficient FANCD2 deubiquitination by the USP1-UAF1 complex is DNA-dependent and requires DNA binding by UAF1; the DNA-binding activity of the UAF1-associated protein RAD51AP1 can substitute for UAF1 DNA binding in FANCD2 deubiquitination in reconstituted biochemical systems. In vitro reconstituted deubiquitination assay with purified components, UAF1/RAD51AP1 DNA-binding mutants, cellular assays Nature communications High 31253762
2019 CK2 phosphorylates a cluster of FANCD2 sites to inhibit FANCD2 binding to DNA and thereby prevent FANCD2 recruitment to ICLs and its monoubiquitination in the absence of DNA damage, functioning as a molecular off-switch for the FA pathway. Phosphosite identification, in vitro monoubiquitination assay with phosphomimetic FANCD2, in vivo CK2 inhibition/knockdown, DNA binding assay Cell reports High 31167143
2019 FANCL allosterically activates UBE2T via rewiring its intraresidue network to influence the active site, enabling site-specific FANCD2 monoubiquitination; a basic triad unique to UBE2T engages an acidic patch near the target lysine on FANCD2; this three-dimensional E2-substrate complementarity induced by FANCL is central to site-specific FA pathway ubiquitination. Biochemical reconstitution of ubiquitination, NMR/mutagenesis of UBE2T active site, structure-function analysis Nature chemical biology High 31873223
2020 ATR directly phosphorylates FANCI on S556, S559, and S565 to stabilize its association with DNA and FANCD2; this increased association stimulates ubiquitin conjugation to both FANCI and FANCD2 but also inhibits USP1-UAF1-mediated deubiquitination; S559 and S565 are particularly important for protecting the complex from deubiquitination. In vitro reconstitution with recombinant proteins, phosphomimetic/phosphodead FANCI mutants, ATR kinase assay Frontiers in cell and developmental biology High 32117957
2020 Ubiquitination of FANCD2 promotes a conformational change in the ID2 complex that increases affinity for dsDNA via formation of a secondary 'Arm' ID2 interface that encircles DNA; ubiquitination of FANCI protects ubiquitin on FANCD2 from USP1-UAF1 deubiquitination via hydrophobic residues of FANCI's ubiquitin. Cryo-EM, biochemical ubiquitination and DNA binding assays, mutagenesis EMBO reports High 32510829
2021 Crystal structures of USP1-UAF1 and cryo-EM reconstruction of USP1-UAF1 bound to monoubiquitinated FANCI-FANCD2 reveal that UAF1 makes an extensive interface with FANCI (confirmed by mutagenesis) driving conformational changes in the substrate; the N-terminus of USP1 harbors a FANCD2-specific binding sequence required for deubiquitination of K561 on FANCD2 but not required for PCNA or FANCI deubiquitination. X-ray crystallography of USP1-UAF1, cryo-EM of USP1-UAF1-monoUb-FANCI-FANCD2, mutagenesis, in vitro deubiquitination reconstitution Nature structural & molecular biology High 33795880
2022 ATR-mediated phosphomimetic substitutions in FANCI cause FANCD2-FANCI to close around DNA independently of the FA core complex; phosphomimetic mutations destabilize the open state and alter conformational dynamics without substantially altering DNA binding affinity, demonstrating that phosphorylation primes the clamp for ubiquitination. Cryo-EM structures of phosphomimetic FANCD2-FANCI complexes, DNA binding assays Nature structural & molecular biology High 36050501
2023 Purified FANCD2 N-terminal domain directly binds and inhibits DNA2 nuclease activity; independently of FANCI dimerization, FANCD2 stabilizes RAD51 filaments to inhibit DNA2, MRE11, and EXO1; FANCD2-stabilized RAD51 filaments stimulate RAD51 strand exchange activity, revealing FANCD2 as a RAD51 mediator. In vitro nuclease inhibition assay with purified FANCD2 and DNA2/MRE11/EXO1, RAD51 filament stabilization assay, strand exchange assay Nucleic acids research High 37526271
2024 FANCD2-FANCI is a sliding clamp that diffuses on dsDNA; it stalls specifically at ssDNA-dsDNA junctions (structures present at stalled replication forks); cryo-EM structures show stalled D2-I makes distinct interactions with ss-dsDNA junctions compared to sliding D2-I, providing a unified mechanism for how D2-I surveys DNA and identifies stalled fork structures. Single-molecule imaging (DNA-tethered diffusion assay), cryo-EM structures of D2-I on DNA substrates Nature High 39085614
2024 SRSF1 physically interacts with FANCD2 and together they suppress R-loop formation via mRNA export regulation; SRSF1 stimulates FANCD2 monoubiquitination in an RNA-dependent fashion; FANCD2 monoubiquitination is required for assembly of the SRSF1-NXF1 nuclear export complex; cancer-associated SRSF1 mutants fail to interact with FANCD2, leading to impaired monoubiquitination, decreased mRNA export, and R-loop accumulation. Co-immunoprecipitation, RNA-dependent interaction assay, mRNA export assay, monoubiquitination assay, siRNA depletion, cancer mutant analysis Cell reports Medium 38165804

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA repair. Cell 586 17412408
2002 S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51. Blood 386 12239151
2004 ATR couples FANCD2 monoubiquitination to the DNA-damage response. Genes & development 331 15314022
2001 Positional cloning of a novel Fanconi anemia gene, FANCD2. Molecular cell 326 11239453
2014 XPF-ERCC1 acts in Unhooking DNA interstrand crosslinks in cooperation with FANCD2 and FANCP/SLX4. Molecular cell 255 24726325
2010 Identification of KIAA1018/FAN1, a DNA repair nuclease recruited to DNA damage by monoubiquitinated FANCD2. Cell 251 20603015
2002 Interaction of FANCD2 and NBS1 in the DNA damage response. Nature cell biology 200 12447395
2013 FANCD2 binds MCM proteins and controls replisome function upon activation of s phase checkpoint signaling. Molecular cell 199 23993743
2004 The DNA crosslink-induced S-phase checkpoint depends on ATR-CHK1 and ATR-NBS1-FANCD2 pathways. The EMBO journal 177 14988723
2016 FANCD2 Maintains Fork Stability in BRCA1/2-Deficient Tumors and Promotes Alternative End-Joining DNA Repair. Cell reports 166 27264184
2007 Deubiquitination of FANCD2 is required for DNA crosslink repair. Molecular cell 165 18082605
2016 FANCD2 protects against bone marrow injury from ferroptosis. Biochemical and biophysical research communications 161 27773819
2004 Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways. Human molecular genetics 159 15115758
2016 FANCD2 Facilitates Replication through Common Fragile Sites. Molecular cell 146 27768874
2003 Menin associates with FANCD2, a protein involved in repair of DNA damage. Cancer research 128 12874027
2011 Structure of the FANCI-FANCD2 complex: insights into the Fanconi anemia DNA repair pathway. Science (New York, N.Y.) 125 21764741
2005 Fanconi anemia protein FANCD2 promotes immunoglobulin gene conversion and DNA repair through a mechanism related to homologous recombination. Molecular and cellular biology 115 15601828
2009 Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M. Blood 114 19423727
2003 BRCA1-independent ubiquitination of FANCD2. Molecular cell 112 12887909
2004 Regulated interaction of the Fanconi anemia protein, FANCD2, with chromatin. Blood 110 15454491
2016 Ubiquitinated Fancd2 recruits Fan1 to stalled replication forks to prevent genome instability. Science (New York, N.Y.) 105 26797144
2014 The genetic and biochemical basis of FANCD2 monoubiquitination. Molecular cell 102 24905007
2020 FANCD2-FANCI is a clamp stabilized on DNA by monoubiquitination of FANCD2 during DNA repair. Nature structural & molecular biology 99 32066963
2003 Knockdown of zebrafish Fancd2 causes developmental abnormalities via p53-dependent apoptosis. Developmental cell 98 14667412
2006 Phosphorylation of FANCD2 on two novel sites is required for mitomycin C resistance. Molecular and cellular biology 97 16943440
2010 Hematopoietic stem cell defects in mice with deficiency of Fancd2 or Usp1. Stem cells (Dayton, Ohio) 96 20506303
2016 FANCD2 limits replication stress and genome instability in cells lacking BRCA2. Nature structural & molecular biology 78 27322732
2014 FANCD2 binds CtIP and regulates DNA-end resection during DNA interstrand crosslink repair. Cell reports 77 24794430
2014 FANCD2 and CtIP cooperate to repair DNA interstrand crosslinks. Cell reports 76 24794434
2007 UBE2T, the Fanconi anemia core complex, and FANCD2 are recruited independently to chromatin: a basis for the regulation of FANCD2 monoubiquitination. Molecular and cellular biology 76 17938197
2015 UHRF1 is a sensor for DNA interstrand crosslinks and recruits FANCD2 to initiate the Fanconi anemia pathway. Cell reports 72 25801034
2019 Binding of FANCI-FANCD2 Complex to RNA and R-Loops Stimulates Robust FANCD2 Monoubiquitination. Cell reports 71 30650351
2014 CtIP mediates replication fork recovery in a FANCD2-regulated manner. Human molecular genetics 70 24556218
2011 The E3 ubiquitin ligase RAD18 regulates ubiquitylation and chromatin loading of FANCD2 and FANCI. Blood 70 21355096
2008 FANCG promotes formation of a newly identified protein complex containing BRCA2, FANCD2 and XRCC3. Oncogene 69 18212739
2012 DNA robustly stimulates FANCD2 monoubiquitylation in the complex with FANCI. Nucleic acids research 68 22287633
2009 A role for monoubiquitinated FANCD2 at telomeres in ALT cells. Nucleic acids research 68 19129235
2018 Replication stress induces accumulation of FANCD2 at central region of large fragile genes. Nucleic acids research 67 29394375
2014 Regulation of FANCD2 and FANCI monoubiquitination by their interaction and by DNA. Nucleic acids research 66 24623813
2013 mTOR regulates DNA damage response through NF-κB-mediated FANCD2 pathway in hematopoietic cells. Leukemia 66 23538752
2016 The FANCD2-FANCI complex is recruited to DNA interstrand crosslinks before monoubiquitination of FANCD2. Nature communications 65 27405460
2015 FANCD2, FANCJ and BRCA2 cooperate to promote replication fork recovery independently of the Fanconi Anemia core complex. Cell cycle (Georgetown, Tex.) 63 25659033
2016 BRCA1/FANCD2/BRG1-Driven DNA Repair Stabilizes the Differentiation State of Human Mammary Epithelial Cells. Molecular cell 62 27373334
2018 FANCD2 protects genome stability by recruiting RNA processing enzymes to resolve R-loops during mild replication stress. The FEBS journal 61 30431240
2019 DNA requirement in FANCD2 deubiquitination by USP1-UAF1-RAD51AP1 in the Fanconi anemia DNA damage response. Nature communications 55 31253762
2013 FANCD2 activates transcription of TAp63 and suppresses tumorigenesis. Molecular cell 53 23806336
2009 FANCI protein binds to DNA and interacts with FANCD2 to recognize branched structures. The Journal of biological chemistry 53 19561358
2009 MRE11-RAD50-NBS1 is a critical regulator of FANCD2 stability and function during DNA double-strand break repair. The EMBO journal 52 19609304
2017 FANCD2 and DNA Damage. International journal of molecular sciences 50 28825622
2012 Fanconi anemia proteins FANCD2 and FANCI exhibit different DNA damage responses during S-phase. Nucleic acids research 49 22753026
2013 Recruitment of DNA polymerase eta by FANCD2 in the early response to DNA damage. Cell cycle (Georgetown, Tex.) 47 23388460
2021 Structural basis of FANCD2 deubiquitination by USP1-UAF1. Nature structural & molecular biology 45 33795880
2016 FANCD2 limits BLM-dependent telomere instability in the alternative lengthening of telomeres pathway. Human molecular genetics 42 27427384
2015 FANCD2 and REV1 cooperate in the protection of nascent DNA strands in response to replication stress. Nucleic acids research 42 26187992
2016 FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5'-DNA end. Nucleic acids research 41 27694619
2005 Mutation analysis of FANCD2, BRIP1/BACH1, LMO4 and SFN in familial breast cancer. Breast cancer research : BCR 41 16280053
2017 FANCD2 Binds Human Papillomavirus Genomes and Associates with a Distinct Set of DNA Repair Proteins to Regulate Viral Replication. mBio 40 28196964
2019 A Fanci knockout mouse model reveals common and distinct functions for FANCI and FANCD2. Nucleic acids research 38 31219578
2009 The Fanconi anemia protein FANCM is controlled by FANCD2 and the ATR/ATM pathways. The Journal of biological chemistry 38 19633289
2020 Differential functions of FANCI and FANCD2 ubiquitination stabilize ID2 complex on DNA. EMBO reports 37 32510829
2007 Loss of expression of FANCD2 protein in sporadic and hereditary breast cancer. Breast cancer research and treatment 37 17333336
2023 FANCD2 inhibits ferroptosis by regulating the JAK2/STAT3 pathway in osteosarcoma. BMC cancer 36 36814203
2017 Fancd2 in vivo interaction network reveals a non-canonical role in mitochondrial function. Scientific reports 36 28378742
2017 FANCI and FANCD2 have common as well as independent functions during the cellular replication stress response. Nucleic acids research 34 29059323
2014 FANCD2 re-expression is associated with glioma grade and chemical inhibition of the Fanconi Anaemia pathway sensitises gliomas to chemotherapeutic agents. Oncotarget 34 25071006
2010 Significance of the Fanconi anemia FANCD2 protein in sporadic and metastatic human breast cancer. The American journal of pathology 33 20363922
2007 DNA structure-induced recruitment and activation of the Fanconi anemia pathway protein FANCD2. Molecular and cellular biology 32 17420278
2006 Drosophila homologs of FANCD2 and FANCL function in DNA repair. DNA repair 32 16860002
2019 Phosphorylation of FANCD2 Inhibits the FANCD2/FANCI Complex and Suppresses the Fanconi Anemia Pathway in the Absence of DNA Damage. Cell reports 31 31167143
2007 FANCD2 monoubiquitination provides a link between the HHR6 and FA-BRCA pathways. Cell cycle (Georgetown, Tex.) 31 18277096
2020 ATR-Mediated FANCI Phosphorylation Regulates Both Ubiquitination and Deubiquitination of FANCD2. Frontiers in cell and developmental biology 30 32117957
2024 The FANCI/FANCD2 complex links DNA damage response to R-loop regulation through SRSF1-mediated mRNA export. Cell reports 29 38165804
2021 Mechanism, specificity, and function of FANCD2-FANCI ubiquitination and deubiquitination. The FEBS journal 29 34137174
2007 A requirement of FancL and FancD2 monoubiquitination in DNA repair. Genes to cells : devoted to molecular & cellular mechanisms 29 17352736
2019 High-risk human papillomavirus oncogenes disrupt the Fanconi anemia DNA repair pathway by impairing localization and de-ubiquitination of FancD2. PLoS pathogens 27 30818369
2010 UBE2W interacts with FANCL and regulates the monoubiquitination of Fanconi anemia protein FANCD2. Molecules and cells 26 21229326
2022 The DNA-damage kinase ATR activates the FANCD2-FANCI clamp by priming it for ubiquitination. Nature structural & molecular biology 25 36050501
2020 FANCD2 Confers a Malignant Phenotype in Esophageal Squamous Cell Carcinoma by Regulating Cell Cycle Progression. Cancers 25 32906798
2019 Clinical importance of FANCD2, BRIP1, BRCA1, BRCA2 and FANCF expression in ovarian carcinomas. Cancer biology & therapy 25 30822218
2017 Overlooked FANCD2 variant encodes a promising, portent tumor suppressor, and alternative polyadenylation contributes to its expression. Oncotarget 25 28157704
2017 Involvement of FANCD2 in Energy Metabolism via ATP5α. Scientific reports 25 28687786
2012 Regulation of the Fanconi anemia pathway by a CUE ubiquitin-binding domain in the FANCD2 protein. Blood 25 22855611
2018 Specificity for deubiquitination of monoubiquitinated FANCD2 is driven by the N-terminus of USP1. Life science alliance 24 30456385
2024 FANCD2-FANCI surveys DNA and recognizes double- to single-stranded junctions. Nature 23 39085614
2022 Comprehensive analysis of the autophagy-dependent ferroptosis-related gene FANCD2 in lung adenocarcinoma. BMC cancer 23 35236309
2019 Allosteric mechanism for site-specific ubiquitination of FANCD2. Nature chemical biology 23 31873223
2010 FANCJ/BRIP1 recruitment and regulation of FANCD2 in DNA damage responses. Chromosoma 23 20676667
2019 Nuclear receptors regulate alternative lengthening of telomeres through a novel noncanonical FANCD2 pathway. Science advances 22 31633027
2017 Fanconi anemia FANCD2 and FANCI proteins regulate the nuclear dynamics of splicing factors. The Journal of cell biology 22 29030393
2023 FANCD2 and RAD51 recombinase directly inhibit DNA2 nuclease at stalled replication forks and FANCD2 acts as a novel RAD51 mediator in strand exchange to promote genome stability. Nucleic acids research 21 37526271
2023 LncRNA SNHG1 upregulates FANCD2 and G6PD to suppress ferroptosis by sponging miR-199a-5p/3p in hepatocellular carcinoma. Drug discoveries & therapeutics 21 37599085
2022 FANCD2 promotes mitotic rescue from transcription-mediated replication stress in SETX-deficient cancer cells. Communications biology 21 36543851
2021 FANCD2 modulates the mitochondrial stress response to prevent common fragile site instability. Communications biology 21 33514811
2016 Chromosomal Integrity after UV Irradiation Requires FANCD2-Mediated Repair of Double Strand Breaks. PLoS genetics 20 26765540
2015 FANCD2 influences replication fork processes and genome stability in response to clustered DSBs. Cell cycle (Georgetown, Tex.) 20 26083937
2012 Heterozygote FANCD2 mutations associated with childhood T Cell ALL and testicular seminoma. Familial cancer 20 22829014
2006 Developmental stage- and DNA damage-specific functions of C. elegans FANCD2. Biochemical and biophysical research communications 20 17126808
2014 The Fanconi anemia proteins FANCD2 and FANCJ interact and regulate each other's chromatin localization. The Journal of biological chemistry 19 25070891
2009 FANCD2 hurdles the DNA interstrand crosslink. Cell 19 20064367
2023 DNA repair protein FANCD2 has both ubiquitination-dependent and ubiquitination-independent functions during germ cell development. The Journal of biological chemistry 18 36642183

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