Affinage

DDX11

ATP-dependent DNA helicase DDX11 · UniProt Q96FC9

Length
970 aa
Mass
108.3 kDa
Annotated
2026-06-09
76 papers in source corpus 31 papers cited in narrative 31 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

DDX11 (ChlR1) is an iron-sulfur cluster-containing, ATP-dependent 5'-to-3' DNA helicase that couples DNA replication to the establishment of sister chromatid cohesion and to the repair of replication-blocking lesions (PMID:18499658, PMID:17105772). The enzyme requires a 5' single-stranded loading region and unwinds duplex DNA as well as the secondary structures that obstruct forks—G-quadruplexes, D-loops, and DNA triplexes—the latter being a preferred substrate (PMID:18499658, PMID:25561740). Catalysis depends on an intact Fe-S cluster and on the Q-motif and Fe-S-region residues (Q23, R263), which are needed for DNA binding and DNA-stimulated ATP hydrolysis (PMID:32071282, PMID:26474416, PMID:23033317). At the replication fork, DDX11 localizes to nascent DNA and acts with Timeless—which binds it directly and stimulates its unwinding up to 10-fold—and with the Ctf18-RFC clamp loader, PCNA, Fen1, and DNA polymerase delta to clear obstacles ahead of the polymerase and generate ssDNA (PMID:30303954, PMID:26503245, PMID:18499658, PMID:32071282). Through these contacts DDX11 physically engages cohesin (Smc1, Smc3, Scc1) and promotes its loading onto replicating chromatin, collaborating with CTF18 to maintain chromatin-bound cohesin against WAPL-mediated unloading (PMID:17105772, PMID:30303954, PMID:34503989). In genome maintenance, DDX11 functions downstream of 53BP1 in homologous recombination, assisting end resection and RPA/RAD51 loading nonredundantly with BRCA1/2, such that its loss sensitizes cells to PARP inhibitors and crosslinking agents (PMID:33879618, PMID:30061412, PMID:23797032). Biallelic loss-of-function mutations in DDX11 cause Warsaw breakage syndrome, a cohesinopathy combining drug-induced chromosomal breakage with sister chromatid cohesion defects (PMID:20137776). Beyond replication and repair, DDX11 binds active rDNA and supports RNA polymerase I transcription (PMID:26089203), organizes constitutive heterochromatin (PMID:21854770), and has reported roles in autophagosome biogenesis and RIG-I/MAVS innate immune signaling (PMID:40413757, PMID:39470258).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2006 High

    Established that human DDX11/ChlR1 is a cohesion factor in mammalian cells, linking it physically to the cohesin complex and answering whether it has a mitotic chromosome-segregation role.

    Evidence RNAi depletion with mitotic phenotyping, immunofluorescence, and Co-IP with cohesin subunits in human cells

    PMID:17105772

    Open questions at the time
    • Did not define the enzymatic activity underlying cohesion
    • Mechanism of cohesin loading not addressed
  2. 2006 High

    Identified a host-pathogen use of DDX11, showing papillomavirus E2 hijacks it to tether viral genomes to mitotic chromosomes.

    Evidence Co-IP, E2 W130R mutagenesis, RNAi, and episome maintenance assays

    PMID:17189189

    Open questions at the time
    • Whether E2 tethering reflects a normal DDX11 chromatin function was unclear
    • Cell-cycle timing of the interaction not defined
  3. 2007 High

    Demonstrated organismal requirement and the cohesin-loading defect underlying DDX11 loss, showing cohesin binds chromatin more loosely without it.

    Evidence Ddx11 knockout mouse plus siRNA in HeLa with chromosome spreads, FACS, and cohesin chromatin-binding assays

    PMID:17611414

    Open questions at the time
    • Did not establish how DDX11 helicase activity promotes cohesin loading
    • Coupling to replication not yet shown
  4. 2008 High

    Reconstituted DDX11 as a 5'-to-3' ATP-dependent helicase and placed it among replication-fork factors, answering its biochemical identity.

    Evidence In vitro ATPase/helicase assays of purified protein with pulldowns against Ctf18-RFC, PCNA, and Fen1

    PMID:18499658

    Open questions at the time
    • Physiological substrates at forks not yet defined
    • Direct link from helicase activity to cohesion remained inferential
  5. 2010 Medium

    Connected DDX11 to human disease, defining Warsaw breakage syndrome at the interface of cohesion and DNA repair.

    Evidence Patient genetics with cytogenetic breakage and cohesion assays

    PMID:20137776

    Open questions at the time
    • Single patient
    • Did not resolve which DDX11 catalytic step is disease-critical
  6. 2012 High

    Showed a disease mutation (R263Q) acts by impairing DNA binding and DNA-stimulated ATP hydrolysis, pinpointing the Fe-S region as functionally essential.

    Evidence In vitro helicase, ATPase, and DNA-binding assays of recombinant WT vs R263Q

    PMID:23033317

    Open questions at the time
    • Direct role of the Fe-S cluster itself not yet dissected
    • Structural basis not resolved
  7. 2015 High

    Defined the Timeless-DDX11 axis and the substrate repertoire (forks, G4, D-loops, triplexes), establishing how DDX11 unwinding is stimulated and which structures it resolves at forks.

    Evidence SPR, in vitro stimulation/EMSA, DNA fiber epistasis, and triplex/G4 helicase assays with the R263Q mutant

    PMID:25561740 PMID:26503245

    Open questions at the time
    • In vivo contribution of each substrate class not separately quantified
    • How Timeless enhances DNA binding mechanistically unresolved
  8. 2015 High

    Mapped catalytic determinants, showing the Q-motif Q23 governs DNA binding/helicase activity independent of ATP binding and that DDX11 acts as a monomer.

    Evidence Mutagenesis with helicase, ATPase, ATP-binding, thermal shift, and proteolysis assays

    PMID:26474416

    Open questions at the time
    • Full structural model absent
    • Coupling of ATP binding to unwinding not detailed
  9. 2015 Medium

    Extended DDX11 function to rDNA, identifying a nucleolar role supporting Pol I transcription and heterochromatin restriction at rDNA.

    Evidence Immunofluorescence, ChIP, Co-IP with UBF/Pol I, knockdown, and zebrafish morpholino with WABS-mutant analysis

    PMID:26089203

    Open questions at the time
    • Whether the helicase acts directly on rDNA structures unresolved
    • Relationship to its cohesion role unclear
  10. 2011 Medium

    Linked DDX11 to chromatin architecture, showing it is required for heterochromatin organization and centromere clustering.

    Evidence siRNA and KO-cell IF, ChIP for HP1α/H3K9me3, bisulfite methylation, and MNase assays

    PMID:21854770

    Open questions at the time
    • Mechanistic basis of heterochromatin defects not defined
    • Single lab
  11. 2018 High

    Resolved how DDX11 loads cohesin, showing a Timeless-binding motif targets it to nascent DNA where it directly contacts cohesin to promote cohesin association during replication.

    Evidence Co-IP, motif mutagenesis, SIRF/iPOND nascent-DNA localization, and in vitro binding of recombinant cohesin with DDX11

    PMID:30303954

    Open questions at the time
    • Whether cohesin loading requires unwinding catalysis not fully separated
    • Stoichiometry of the DDX11-cohesin contact unknown
  12. 2018 High

    Placed DDX11 in postreplicative HR/ICL repair as an FA-pathway backup acting with the 9-1-1 clamp and RAD17.

    Evidence DT40 genetic epistasis, ICL sensitivity, DNA fiber, and Ig diversification assays

    PMID:30061412

    Open questions at the time
    • Direct enzymatic step in HR not defined here
    • Human relevance shown only indirectly
  13. 2020 High

    Demonstrated the Fe-S cluster is required for activity and that DDX11 clears obstacles ahead of Pol delta to generate ssDNA needed for checkpoint signaling.

    Evidence In vitro Pol delta obstacle-removal assay, Fe-S mutagenesis, Co-IP with Pol delta/WDHD1, RPA fractionation, and CHK1 phosphorylation

    PMID:32071282

    Open questions at the time
    • Nature of in vivo obstacles not specified
    • WDHD1 role mechanistically undefined
  14. 2020 High

    Tied G-quadruplex traversal to the Timeless-DDX11 axis and confirmed the helicase domain is essential for cohesion and G4-stabilizer resistance, distinguishing DDX11 from FANCJ.

    Evidence G4 binding/replication assays, co-depletion genetic interactions, and CRISPR KO with helicase-domain rescue in RPE1-TERT cells

    PMID:32705708 PMID:32855419

    Open questions at the time
    • Relative in vivo G4 vs triplex contributions unresolved
    • TP53-dependence of proliferation defect mechanistically unexplained
  15. 2020 High

    Positioned DDX11 in homology-directed repair downstream of 53BP1, mediating RPA/RAD51 loading nonredundantly with BRCA1/2 and defining a chemosensitization vulnerability.

    Evidence Knockdown with RAD51/RPA focus and resection assays, epistasis with 53BP1/BRCA1/2, and PARPi/cisplatin sensitivity

    PMID:33879618

    Open questions at the time
    • Direct enzymatic substrate during resection not defined
    • How DDX11 acts relative to BRCA pathway molecularly unresolved
  16. 2020 Medium

    Defined non-redundant ESCO2-DDX11 and WAPL-dependent relationships in residual cohesion in patient cells.

    Evidence Patient-derived cells, combinatorial siRNA with WAPL rescue, DNA-binding mutant complementation, and fiber assays

    PMID:31935221

    Open questions at the time
    • Single lab
    • Mechanistic basis of ESCO2 specificity not resolved
  17. 2021 High

    Precisely placed DDX11 in cohesin homeostasis, showing it and CTF18 maintain chromatin-bound cohesin against WAPL unloading rather than via ESCO acetyltransferases.

    Evidence DT40 double-KO epistasis with WAPL-depletion and ESCO1/2-overexpression rescue and cohesin loading assays

    PMID:34503989

    Open questions at the time
    • How DDX11 counteracts WAPL biochemically unknown
    • Direct DDX11 action on cohesin ring not shown
  18. 2024 Medium

    Confirmed cohesion machinery as the dominant genetic dependency of DDX11-deficient cells, identifying STAG2 and HASPIN synthetic lethality.

    Evidence Genome-wide CRISPR dropout screen with validation of specific hits

    PMID:38478595

    Open questions at the time
    • Mechanism of HASPIN dependency not explained
    • Therapeutic translation untested
  19. 2024 Medium

    Refined the HR role mechanistically, showing ATM phosphorylation of DDX11 at S237 enables RAD51 recruitment via the BRCA2-RAD51 interaction in hepatocellular carcinoma.

    Evidence Co-IP, CRISPR knock-in reversion of Q238H, ATM phosphorylation assay, and RAD51 focus formation

    PMID:38007537

    Open questions at the time
    • Single tumor context
    • How phosphorylation alters DDX11 activity unclear
  20. 2024 Medium

    Proposed a cytosolic immune role, identifying DDX11 as a co-sensor enhancing RIG-I dsRNA binding and RIG-I-MAVS signaling.

    Evidence siRNA/CRISPR KO, IFN-β reporter, Co-IP with RIG-I/MAVS, and STING/RIG-I/MAVS epistasis

    PMID:39470258

    Open questions at the time
    • Novel function with limited replication
    • Relationship to nuclear helicase activity unknown
  21. 2025 Medium

    Identified a cytoplasmic role in macroautophagy, with DDX11 supporting LC3 lipidation and ATG16L1 trafficking via interaction with SQSTM1.

    Evidence CRISPR KO in RPE-1, tandem LC3 reporter imaging, ATG16L1 trafficking, HTT aggregate clearance, and PLA with SQSTM1

    PMID:40413757

    Open questions at the time
    • Whether helicase activity is required for autophagy unknown
    • Single lab, novel function

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single Fe-S helicase mechanistically partitions among its replication/cohesion, DNA-repair, nucleolar, heterochromatin, autophagy, and innate-immune roles, and whether the non-genomic functions depend on its catalytic activity.
  • No structural model of DDX11 reported in the corpus
  • Catalytic requirement for autophagy and immune signaling untested
  • Regulation directing DDX11 between nuclear and cytoplasmic roles unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 3 GO:0140097 catalytic activity, acting on DNA 3 GO:0140657 ATP-dependent activity 3 GO:0016787 hydrolase activity 2 GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 2 GO:0005694 chromosome 2 GO:0005829 cytosol 2 GO:0005730 nucleolus 1
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-69306 DNA Replication 2 R-HSA-73894 DNA Repair 2 R-HSA-168256 Immune System 1 R-HSA-4839726 Chromatin organization 1 R-HSA-74160 Gene expression (Transcription) 1 R-HSA-9612973 Autophagy 1
Partners
EZH2FEN1MAVSPARP1PCNARIG-ITIMELESSWDHD1
Complex memberships
cohesin

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Human ChlR1 (DDX11) is required for sister chromatid cohesion in mammalian cells. ChlR1 diffusely coats mitotic chromatin in prophase then translocates to spindle poles at metaphase. RNAi depletion causes mitotic failure, pro-metaphase arrest, and increased centromeric chromatid separation. ChlR1 co-immunoprecipitates with cohesin subunits Scc1, Smc1, and Smc3. RNAi knockdown, immunofluorescence localization, Co-IP with cohesin subunits, chromosome spread analysis Journal of cell science High 17105772
2008 Purified human ChlR1 possesses DNA-dependent ATPase and 5'-to-3' helicase activities, requires a 5' single-stranded region for loading, and can unwind duplexes up to 100 bp (extended to 500 bp by RPA or Ctf18-RFC). ChlR1 physically interacts with the Ctf18-RFC complex, PCNA, and Fen1; the ChlR1-Fen1 interaction stimulates Fen1 flap endonuclease activity. Depletion of either ChlR1 or Fen1 by siRNA causes precocious sister chromatid separation. Purification from 293 cells, in vitro ATPase and helicase assays, Co-IP/pulldown with Ctf18-RFC/PCNA/Fen1, siRNA knockdown with chromatid cohesion readout The Journal of biological chemistry High 18499658
2006 Papillomavirus E2 protein binds ChlR1 (DDX11), and this interaction is required for loading E2 onto mitotic chromosomes. An E2 W130R mutation abolishes ChlR1 binding and correspondingly prevents E2 association with mitotic chromosomes; viral genomes encoding W130R are not episomally maintained. RNAi depletion of ChlR1 significantly reduces E2 localization to mitotic chromosomes. Co-IP, site-directed mutagenesis of E2 (W130R), RNAi knockdown, immunofluorescence localization, episome maintenance assay Molecular cell High 17189189
2007 Loss of mouse Ddx11 causes embryonic lethality at E10.5 with placental malformation, G2/M cell cycle delay, increased chromosome missegregation, decreased sister chromatid cohesion at centromeres and arms, and increased aneuploidy. ChlR1 is required for proper cohesin complex binding to both centromere and chromosome arms; cohesin binds more loosely to chromatin in ChlR1-depleted cells. Ddx11 knockout mouse, siRNA depletion in HeLa cells, chromosome spreads, FACS cell cycle analysis, immunofluorescence, cohesin chromatin binding assay Cell cycle (Georgetown, Tex.) High 17611414
2010 Biallelic loss-of-function mutations in DDX11 cause Warsaw breakage syndrome, a cohesinopathy with features of both Fanconi anemia (drug-induced chromosomal breakage) and Roberts syndrome (sister chromatid cohesion defects), establishing DDX11 functions at the interface of DNA repair and sister chromatid cohesion. Patient genetic analysis, cytogenetic analysis (MMC-induced breakage, sister chromatid cohesion assay) American journal of human genetics Medium 20137776
2012 A homozygous p.R263Q mutation in DDX11 impairs helicase activity by perturbing DNA binding and DNA-dependent ATP hydrolysis, while leaving overall protein structure intact, confirming the functional importance of the Fe-S domain region for DDX11 enzymatic activity. Purification of recombinant wild-type and p.R263Q DDX11, in vitro helicase assay, ATPase assay, DNA binding assay Human mutation High 23033317
2015 Tim (Timeless) physically interacts with DDX11 (confirmed by surface plasmon resonance), stimulates DDX11 unwinding activity up to 10-fold on forked DNA and 4-5-fold on G-quadruplex and D-loop substrates by enhancing DDX11 DNA binding. Tim and DDX11 are epistatic for replication fork progression and fork restart after hydroxyurea treatment; their chromatin association increases after hydroxyurea exposure. Surface plasmon resonance, in vitro helicase stimulation assay, EMSA, DNA fiber assay, siRNA co-depletion epistasis, chromatin fractionation Co-IP Nucleic acids research High 26503245
2015 DDX11/ChlR1 efficiently unwinds both intermolecular and intramolecular DNA triplex substrates in an ATP-dependent manner; triplex DNA is a preferred substrate compared to replication fork and G-quadruplex DNA. The WABS patient mutant (R263Q) fails to unwind triplexes. ChlR1-depleted cells show increased triplex DNA content and double-strand breaks upon treatment with a triplex-stabilizing compound, while FANCJ-deficient cells do not. In vitro helicase assay with triplex substrates, recombinant protein purification, siRNA depletion, immunofluorescence for triplex content and DSBs The Journal of biological chemistry High 25561740
2015 The Q motif glutamine (Q23) of ChlR1 is required for DNA binding and helicase activity but not ATP binding; Q23A mutant shows impaired ATPase activity and reduced DNA binding while retaining normal ATP binding and similar overall structure. ChlR1 functions as a monomer in solution. Site-directed mutagenesis, purification of recombinant ChlR1 from HEK293T, in vitro helicase assay, ATPase assay, ATP binding assay, thermal shift assay, partial proteolysis PloS one High 26474416
2015 DDX11 is a nucleolar protein that binds hypomethylated active rDNA gene loci, where it interacts with upstream binding factor (UBF) and RNA polymerase I. DDX11 knockdown increases heterochromatin at rDNA loci, reduces UBF activity and recruitment of UBF and RPA194 to rDNA promoters, suppresses rRNA transcription, and inhibits cell growth. WABS-derived mutants (R263Q, K897del) and Fe-S deletion show reduced rDNA promoter binding and ATPase activity. Immunofluorescence, ChIP, Co-IP with UBF and Pol I, siRNA knockdown, rRNA transcription assay, recombinant mutant protein analysis, zebrafish morpholino knockdown Human molecular genetics Medium 26089203
2011 ChlR1 (DDX11) is required for proper heterochromatin organization; ChlR1-depleted cells show dispersed localization of constitutive heterochromatin, disrupted centromere clustering, decreased HP1α at pericentric regions (by IF and ChIP), modest reduction of H3K9-me3, decreased DNA methylation at major satellite repeats, and decreased chromatin density at telomeres (by MNase assay). siRNA knockdown in HeLa cells, Ddx11-/- mouse embryo cells, immunofluorescence, ChIP for HP1α and H3K9-me3, bisulfite DNA methylation analysis, MNase assay Experimental cell research Medium 21854770
2018 DDX11 interacts with Timeless through a conserved peptide motif; this interaction is critical for sister chromatid cohesion in interphase and mitosis. DDX11 localizes at nascent DNA (SIRF analysis). DDX11 promotes cohesin binding to DNA replication forks in concert with Timeless. Purified recombinant cohesin directly interacts with DDX11 in vitro. Loss of DDX11-Timeless interaction impairs cohesin association with chromatin. Co-IP, peptide motif mutagenesis, immunofluorescence, SIRF assay (nascent DNA localization), iPOND, in vitro binding of recombinant cohesin with DDX11 PLoS genetics High 30303954
2018 In avian DT40 cells, DDX11 functions as a backup for the FA pathway in interstrand crosslink repair. DDX11 acts jointly with the 9-1-1 checkpoint clamp and its loader RAD17 in a postreplicative fashion to promote homologous recombination repair of bulky lesions. DDX11 also facilitates diversification of the chicken Ig-variable gene (hypermutation and gene conversion), processes triggered by programmed abasic sites. DDX11 is not required for intra-S checkpoint activation or efficient fork progression. DT40 genetic knockout, epistasis analysis with 9-1-1/RAD17 mutants, ICL sensitivity assays, DNA fiber assay, Ig gene diversification assay Proceedings of the National Academy of Sciences of the United States of America High 30061412
2020 The iron-sulfur (FeS) cluster in DDX11 is required for DNA binding, ATP hydrolysis, and DNA helicase activity; arginine-263 in the FeS cluster-binding motif affects FeS cluster binding via its positive charge. DDX11 interacts with DNA polymerase delta and WDHD1. In vitro, DDX11 removes DNA obstacles ahead of Pol δ in an ATPase- and FeS-domain-dependent manner, generating single-stranded DNA. DDX11 depletion reduces ssDNA levels, chromatin-bound RPA, and impairs CHK1 phosphorylation at serine-345. In vitro helicase assay with Pol δ, mutagenesis of FeS domain, Co-IP with Pol δ and WDHD1, siRNA depletion, RPA chromatin fractionation, CHK1 phosphorylation assay Life science alliance High 32071282
2020 Timeless harbors a C-terminal G-quadruplex (G4) DNA-binding domain. This domain contributes to processive replication through G4-forming sequences and shows partial redundancy with an adjacent PARP-binding domain. Timeless G4 function requires interaction with and activity of DDX11 helicase. Loss of both Timeless and DDX11 causes epigenetic instability at G4-forming sequences and DNA damage. G4 DNA binding assay, DNA replication assay through G4 sequences, genetic interaction (co-depletion), epigenetic stability assay, DNA damage assay The EMBO journal High 32705708
2020 The DNA helicase domain of DDX11 is essential for sister chromatid cohesion and resistance to G4-stabilizing compounds. G4-stabilizing compounds induce chromosome breaks and cohesion defects that are strongly aggravated by DDX11 inactivation but not FANCJ inactivation. DDX11 deletion in RPE1-TERT cells inhibits proliferation in a TP53-dependent manner and causes chromosome breaks and cohesion defects independent of DDX12p. CRISPR knockout in RPE1-TERT cells, helicase domain mutant complementation, G4 stabilizer treatment, chromosome break assay, cohesion assay, FANCJ comparison Nature communications High 32855419
2020 DDX11 loss causes replication stress and sensitizes cancer cells to PARP inhibitors and platinum drugs. DDX11 acts downstream of 53BP1 to mediate homology-directed repair and RAD51 focus formation in a manner nonredundant with BRCA1 and BRCA2. DDX11 facilitates recombination repair by assisting double-strand break resection and loading of RPA and RAD51 onto ssDNA. DDX11 down-regulation aggravates chemotherapeutic sensitivity of BRCA1/2-mutated cancers and resensitizes drug-resistant BRCA1/2-mutated cells. siRNA/shRNA knockdown, RAD51 and RPA focus formation assay, epistasis with 53BP1 and BRCA1/2, DNA resection assay, PARP inhibitor and cisplatin sensitivity assay Proceedings of the National Academy of Sciences of the United States of America High 33879618
2021 CTF18 and DDX11 act complementarily in sister chromatid cohesion (SCC) and proliferation in DT40 cells. Lethality and cohesion defects of ctf18 ddx11 double mutants are associated with reduced chromatin-bound cohesin and rescued by WAPL depletion (cohesin-removal factor), but not by overexpression of ESCO1/2 acetyltransferases. CTF18 and DDX11 collaborate to maintain sufficient chromatin-loaded cohesin against WAPL-mediated unloading. DT40 double KO genetic epistasis, cohesin chromatin loading assay, WAPL depletion rescue, ESCO1/2 overexpression rescue, chromosome bridge assay Genes & development High 34503989
2020 WABS-derived cells with DDX11 mutations show non-redundant roles for ESCO2 (not ESCO1) in residual SCC; reciprocally, Roberts syndrome (ESCO2-mutant) cells depend on DDX11 for residual cohesion. Synthetic lethality of DDX11 and ESCO2 is rescued by WAPL knockdown. A DNA-binding DDX11 mutant fails to correct SCC in WABS cells, and DDX11 deficiency reduces replication fork speed. Patient-derived cell lines, siRNA combinatorial knockdown, WAPL rescue, DDX11 DNA-binding mutant complementation, DNA fiber assay for fork speed PloS one Medium 31935221
2021 DDX11 interacts with EZH2 in HCC cells and protects EZH2 from ubiquitination-mediated protein degradation, resulting in downregulation of p21. DDX11 knockdown arrests cells at G1 phase and induces p21 without altering p53. E2F1 is identified as an upstream transcriptional regulator of DDX11, forming a positive feedback loop with EZH2. Co-IP (DDX11-EZH2), ubiquitination assay, siRNA knockdown, p21/p53 western blot, E2F1 ChIP and luciferase reporter assay, rescue with p21 siRNA Frontiers in oncology Medium 33614480
2011 BPV-1 E2 and ChlR1 interact during specific phases of the cell cycle, confirmed by FRET in live synchronized cells. The E2-ChlR1 association occurs during DNA replication rather than during mitotic tethering. FRET in live synchronized cells, cell cycle synchronization Virology Medium 21489590
2016 ChlR1 regulates the chromatin and nuclear matrix association of HPV16 E2 during S phase. An HPV16 E2 Y131A mutation reduces ChlR1 binding, decreases the chromatin-bound pool of E2, increases nuclear matrix association in mid-S phase, reduces HPV16 episome copy number at establishment, and prevents episome maintenance upon cell passage. ChlR1 silencing phenocopies the E2 Y131A mutation. Co-IP/binding assay, site-directed mutagenesis (E2 Y131A), subcellular fractionation, cell cycle synchronization, HPV16 life cycle model in primary keratinocytes, siRNA knockdown Journal of virology High 27795438
2013 ChlR1 depletion renders human cells sensitive to cisplatin (interstrand crosslink agent causing stalled replication forks), leads to accumulation of DNA damage and delayed resolution, impairs repair of double-strand breaks induced by I-PpoI endonuclease and bleomycin, and causes significant delays in DNA replication recovery after cisplatin treatment. siRNA depletion, cisplatin/bleomycin sensitivity assay, I-PpoI DSB assay, DNA damage marker (γH2AX) kinetics, DNA replication recovery assay Experimental cell research Medium 23797032
2014 DDX11 (FANCM) was identified as a determinant of PARP inhibitor sensitivity; DDX11-deficient lymphoblastoid cell lines derived from Warsaw breakage syndrome patients show strong sensitivity to PARP inhibitors. PARP inhibitor sensitivity assay in patient-derived DDX11-deficient lymphoblastoid cell lines DNA repair Medium 25583207
2023 DDX11 promotes homologous recombination in hepatocellular carcinoma by facilitating RAD51 recruitment to damaged DNA through the BRCA2-RAD51 interaction. A natural DDX11 Q238H mutation impedes ATM-mediated phosphorylation of DDX11 at serine-237, preventing recruitment of RAD51 to damage sites by disrupting BRCA2-RAD51 interaction. CRISPR knock-in reverting Q238H to wild-type restores HR competence. Co-IP (DDX11-BRCA2-RAD51), CRISPR/Cas9 knock-in, ATM phosphorylation assay, RAD51 focus formation, PARP inhibitor sensitivity assay Oncogene Medium 38007537
2024 DDX11 acts as a novel co-sensor for cytosolic nucleic acids in innate immunity. DDX11 knockdown/knockout attenuates IFN-β production in response to Sendai virus and poly(I:C). DDX11 operates dependent on RIG-I and MAVS (not STING). DDX11 binds nucleic acids and directly interacts with RIG-I and MAVS, enhancing RIG-I dsRNA binding affinity and RIG-I-MAVS binding affinity. DDX11 promotes TANK-binding kinase 1 and IRF3 activation. siRNA/CRISPR KO, IFN-β reporter assay, Co-IP (DDX11-RIG-I, DDX11-MAVS), nucleic acid binding assay, STING/RIG-I/MAVS epistasis knockdown mBio Medium 39470258
2025 DDX11 has a novel cytoplasmic role in regulating macroautophagy. DDX11 knockout in RPE-1 cells impairs autophagosome biogenesis, reduces LC3 lipidation/conversion, impairs ATG16L1-precursor trafficking and maturation, and reduces clearance of mutant HTT aggregates. DDX11 functionally interacts with SQSTM1 (p62) cargo receptor in supporting LC3 modification during autophagosome biogenesis. CRISPR KO in RPE-1 cells, mRFP-GFP-LC3 tandem reporter imaging, LC3 western blot, ATG16L1 trafficking assay, HTTQ74-GFP aggregate clearance assay, proximity ligation assay (DDX11-SQSTM1) Autophagy Medium 40413757
2025 DDX11 interacts with PARP1 (confirmed by Co-IP from proteomic analysis), and this interaction promotes increased poly(ADP-ribosyl)ation (PARylation), facilitating DNA repair and gemcitabine resistance in gallbladder cancer. DDX11 knockdown inhibits cell proliferation and restores gemcitabine sensitivity. Proteomic analysis, Co-IP (DDX11-PARP1), PARylation assay, siRNA knockdown, gemcitabine sensitivity assay Acta biochimica et biophysica Sinica Low 40859772
2024 CRISPR genome-wide screen in DDX11-deficient cells identified a strong enrichment of sister chromatid cohesion genes as genetic dependencies; synthetic lethal relationships confirmed between DDX11 and cohesin subunit STAG2 and kinase HASPIN. Genome-wide CRISPR dropout screen in DDX11-WT vs DDX11-deficient cells, confirmation of STAG2 and HASPIN synthetic lethality G3 (Bethesda, Md.) Medium 38478595
2020 E2F1 transcriptionally activates DDX11 in hepatocellular carcinoma, as demonstrated by ChIP and luciferase reporter assays. DDX11 overexpression promotes HCC cell proliferation, migration, and invasion through activation of the PI3K/AKT/mTOR signaling pathway. ChIP for E2F1 at DDX11 promoter, luciferase reporter assay, DDX11 gain/loss-of-function, PI3K/AKT/mTOR pathway analysis Cell death & disease Low 32332880
2025 DDX11 interacts with ATAD5 (confirmed by co-immunoprecipitation and immunofluorescence co-localization in gallbladder cancer cells). ATAD5 silencing attenuates DDX11-mediated oncogenic effects. The DDX11-ATAD5 complex promotes epithelial-mesenchymal transition (EMT) to facilitate GBC invasion and metastasis. Co-IP, immunofluorescence co-localization, siRNA knockdown of ATAD5, EMT marker analysis, xenograft model CytoJournal Low 41664698

Source papers

Stage 0 corpus · 76 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Warsaw breakage syndrome, a cohesinopathy associated with mutations in the XPD helicase family member DDX11/ChlR1. American journal of human genetics 166 20137776
2006 The DNA helicase ChlR1 is required for sister chromatid cohesion in mammalian cells. Journal of cell science 93 17105772
2008 Studies with the human cohesin establishment factor, ChlR1. Association of ChlR1 with Ctf18-RFC and Fen1. The Journal of biological chemistry 89 18499658
2006 ChlR1 is required for loading papillomavirus E2 onto mitotic chromosomes and viral genome maintenance. Molecular cell 84 17189189
2007 Loss of ChlR1 helicase in mouse causes lethality due to the accumulation of aneuploid cells generated by cohesion defects and placental malformation. Cell cycle (Georgetown, Tex.) 77 17611414
2012 Identification and biochemical characterization of a novel mutation in DDX11 causing Warsaw breakage syndrome. Human mutation 66 23033317
2020 Timeless couples G-quadruplex detection with processing by DDX11 helicase during DNA replication. The EMBO journal 64 32705708
2020 E2F1 mediated DDX11 transcriptional activation promotes hepatocellular carcinoma progression through PI3K/AKT/mTOR pathway. Cell death & disease 61 32332880
2015 Tim/Timeless, a member of the replication fork protection complex, operates with the Warsaw breakage syndrome DNA helicase DDX11 in the same fork recovery pathway. Nucleic acids research 57 26503245
2014 Molecular functions and cellular roles of the ChlR1 (DDX11) helicase defective in the rare cohesinopathy Warsaw breakage syndrome. Cellular and molecular life sciences : CMLS 52 24487782
2020 Warsaw Breakage Syndrome associated DDX11 helicase resolves G-quadruplex structures to support sister chromatid cohesion. Nature communications 49 32855419
2018 Interaction of the Warsaw breakage syndrome DNA helicase DDX11 with the replication fork-protection factor Timeless promotes sister chromatid cohesion. PLoS genetics 48 30303954
2015 A distinct triplex DNA unwinding activity of ChlR1 helicase. The Journal of biological chemistry 46 25561740
2012 The DEAD/DEAH box helicase, DDX11, is essential for the survival of advanced melanomas. Molecular cancer 46 23116066
2019 Long noncoding RNA DDX11-AS1 epigenetically represses LATS2 by interacting with EZH2 and DNMT1 in hepatocellular carcinoma. Biochemical and biophysical research communications 38 31097223
2020 Long non-coding RNA DDX11-AS1 facilitates gastric cancer progression by regulating miR-873-5p/SPC18 axis. Artificial cells, nanomedicine, and biotechnology 34 32054332
2014 DNA helicases FANCM and DDX11 are determinants of PARP inhibitor sensitivity. DNA repair 34 25583207
2018 Warsaw breakage syndrome DDX11 helicase acts jointly with RAD17 in the repair of bulky lesions and replication through abasic sites. Proceedings of the National Academy of Sciences of the United States of America 33 30061412
2020 LncRNA DDX11-AS1: a novel oncogene in human cancer. Human cell 32 32772230
2021 DDX11 loss causes replication stress and pharmacologically exploitable DNA repair defects. Proceedings of the National Academy of Sciences of the United States of America 30 33879618
2020 The long non-coding RNA DDX11-AS1 facilitates cell progression and oxaliplatin resistance via regulating miR-326/IRS1 axis in gastric cancer. European review for medical and pharmacological sciences 29 32271422
2019 Long noncoding RNA DDX11-AS1 induced by YY1 accelerates colorectal cancer progression through targeting miR-873/CLDN7 axis. European review for medical and pharmacological sciences 29 31298324
2020 LncRNA DDX11-AS1 accelerates hepatocellular carcinoma progression via the miR-195-5p/MACC1 pathway. Annals of hepatology 28 32961346
2013 Roles of ChlR1 DNA helicase in replication recovery from DNA damage. Experimental cell research 28 23797032
2020 DDX11-AS1 contributes to osteosarcoma progression via stabilizing DDX11. Life sciences 27 32014424
2018 Molecular and Cellular Functions of the Warsaw Breakage Syndrome DNA Helicase DDX11. Genes 27 30469382
2022 Long non-coding RNA DDX11-AS1 promotes the proliferation and migration of glioma cells by combining with HNRNPC. Molecular therapy. Nucleic acids 26 35614994
2021 Vertebrate CTF18 and DDX11 essential function in cohesion is bypassed by preventing WAPL-mediated cohesin release. Genes & development 25 34503989
2022 Knockdown of long non‑coding RNA DDX11‑AS1 inhibits the proliferation, migration and paclitaxel resistance of breast cancer cells by upregulating microRNA‑497 expression. Molecular medicine reports 23 35169864
2020 LncRNA DDX11-AS1 Promotes Bladder Cancer Occurrence Via Protecting LAMB3 from Downregulation by Sponging miR-2355-5p. Cancer biotherapy & radiopharmaceuticals 23 32412777
2019 The resistance of esophageal cancer cells to paclitaxel can be reduced by the knockdown of long noncoding RNA DDX11-AS1 through TAF1/TOP2A inhibition. American journal of cancer research 23 31720085
2017 DDX11-AS1 as potential therapy targets for human hepatocellular carcinoma. Oncotarget 22 28496001
2015 The Warsaw breakage syndrome-related protein DDX11 is required for ribosomal RNA synthesis and embryonic development. Human molecular genetics 21 26089203
2011 Mammalian ChlR1 has a role in heterochromatin organization. Experimental cell research 21 21854770
2021 An E2F1/DDX11/EZH2 Positive Feedback Loop Promotes Cell Proliferation in Hepatocellular Carcinoma. Frontiers in oncology 19 33614480
2021 Landscape analysis of lncRNAs shows that DDX11-AS1 promotes cell-cycle progression in liver cancer through the PARP1/p53 axis. Cancer letters 19 34371129
2021 LncRNA DDX11 antisense RNA 1 promotes EMT process of esophageal squamous cell carcinoma by sponging miR-30d-5p to regulate SNAI1/ZEB2 expression and Wnt/β-catenin pathway. Bioengineered 19 34866524
2021 The Genome Stability Maintenance DNA Helicase DDX11 and Its Role in Cancer. Genes 17 33802088
2020 The iron-sulfur helicase DDX11 promotes the generation of single-stranded DNA for CHK1 activation. Life science alliance 17 32071282
2020 DDX11-AS1exacerbates bladder cancer progression by enhancing CDK6 expression via suppressing miR-499b-5p. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 17 32422563
2021 Long non-coding RNA DDX11-AS1 promotes esophageal carcinoma cell proliferation and migration through regulating the miR-514b-3p/RBX1 axis. Bioengineered 16 34281459
2020 Non-redundant roles in sister chromatid cohesion of the DNA helicase DDX11 and the SMC3 acetyl transferases ESCO1 and ESCO2. PloS one 16 31935221
2020 Long non-coding RNA DDX11-AS1 promotes non-small cell lung cancer development via regulating PI3K/AKT signalling. Clinical and experimental pharmacology & physiology 16 32298476
2016 The Cellular DNA Helicase ChlR1 Regulates Chromatin and Nuclear Matrix Attachment of the Human Papillomavirus 16 E2 Protein and High-Copy-Number Viral Genome Establishment. Journal of virology 16 27795438
2012 The ENU-induced cetus mutation reveals an essential role of the DNA helicase DDX11 for mesoderm development during early mouse embryogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 15 22678773
2011 In vivo analysis of the cell cycle dependent association of the bovine papillomavirus E2 protein and ChlR1. Virology 15 21489590
2015 The Q Motif Is Involved in DNA Binding but Not ATP Binding in ChlR1 Helicase. PloS one 13 26474416
2023 Targeting DDX11 promotes PARP inhibitor sensitivity in hepatocellular carcinoma by attenuating BRCA2-RAD51 mediated homologous recombination. Oncogene 12 38007537
2022 LncRNA DDX11-AS1 Promotes Chemoresistance through LIN28A-Mediated ATG12 mRNA Stabilization in Breast Cancer. Pharmacology 12 36382664
2021 Silenced lncRNA DDX11-AS1 or up-regulated microRNA-34a-3p inhibits malignant phenotypes of hepatocellular carcinoma cells via suppression of TRAF5. Cancer cell international 12 33752668
2023 DDX11-AS1 modulates DNA damage repair to enhance paclitaxel resistance of lung adenocarcinoma cells. Pharmacogenomics 10 36779347
2021 LncRNA DDX11-AS1 Exerts Oncogenic Roles in Glioma Through Regulating miR-499b-5p/RWDD4 Axis. OncoTargets and therapy 10 33447057
2021 The DEAD/DEAH Box Helicase, DDX11, Is Essential for the Survival of Advanced Clear Cell Renal Cell Carcinoma and Is a Determinant of PARP Inhibitor Sensitivity. Cancers 10 34073906
2021 Role of the DDX11 DNA Helicase in Warsaw Breakage Syndrome Etiology. International journal of molecular sciences 7 33669056
2021 Association between visceral adiposity and DDX11 as a predictor of aggressiveness of small clear-cell renal-cell carcinoma: a prospective clinical trial. Cancer & metabolism 4 33823929
2020 A Timeless Tale: G4 structure recognition by the fork protection complex triggers unwinding by DDX11 helicase. The EMBO journal 4 32790898
2024 Long noncoding RNA DDX11-AS1 represses sorafenib-induced ferroptosis in hepatocellular carcinoma cells via Nrf2-Keap1 pathway. Discover oncology 3 39390130
2024 LncRNA DDX11-AS1 promotes breast cancer progression by targeting the miR-30c-5p/MTDH axis. Scientific reports 3 39501057
2021 Expression of DDX11 and DNM1L at the 12p11 Locus Modulates Systemic Lupus Erythematosus Susceptibility. International journal of molecular sciences 3 34299244
2025 NRF1-Induced lncRNA DDX11-AS1 Contributes to the Progression of Hepatocellular Carcinoma via Activating CA9 Expression and the MEK/ERK Pathway. Journal of hepatocellular carcinoma 2 40356690
2025 Evidence of an unprecedented cytoplasmic function of DDX11, the Warsaw breakage syndrome DNA helicase, in regulating autophagy. Autophagy 2 40413757
2025 DDX11 interacts with PARP1 to facilitate PARylation, thereby promoting gallbladder cancer progression and conferring gemcitabine resistance. Acta biochimica et biophysica Sinica 2 40859772
2024 Helicase protein DDX11 as a novel antiviral factor promoting RIG-I-MAVS-mediated signaling pathway. mBio 2 39470258
2025 Predictive value of long non-coding RNA DDX11-AS1 in inflammatory bowel disease and its effect on intestinal mucosal cell function. Central-European journal of immunology 1 40620651
2024 Mapping of DDX11 genetic interactions defines sister chromatid cohesion as the major dependency. G3 (Bethesda, Md.) 1 38478595
2024 ATPR induces acute promyelocytic leukemia cells differentiation and cycle arrest via the lncRNA CONCR/DDX11/PML-RARα signaling axis. Gene 1 38582263
2024 Prenatal Diagnosis of Warsaw Breakage Syndrome: Fetal Compound Heterozygous Variants in the DDX11 Gene Associated With Growth Restriction, Cerebral, and Extra-Cerebral Malformations. Prenatal diagnosis 1 39428552
2026 DDX11/SKP2 Inhibits Cisplatin Sensitivity in Liver Cancer Cells by Regulating DNA Damage Repair and ER Stress. Applied biochemistry and biotechnology 0 41489706
2026 Computational and Experimental Verification of Cabozantinib Targeting DDX11 to Inhibit DNA Damage Repair in Liver Cancer. ACS omega 0 41696275
2026 ALYREF-mediated RNA 5-methylcytosine modification promotes laryngeal cancer progression via stabilizing DDX11 mRNA. Scientific reports 0 41826389
2026 Genetic characterization of DDX11 variants identified in a Chinese family with Warsaw breakage syndrome. Seizure 0 42107920
2025 Small protein DDX11-AS1-ORF encoded by lncRNA DDX11-AS1 promotes colorectal cancer progression through VEGFA-activated p38-MAPK pathway. American journal of cancer research 0 40371138
2025 Piperlongumine inhibits renal cell carcinoma progression by modulating the DDX11-miR-15b-3p-DLD axis. Translational andrology and urology 0 40376520
2025 Competitive Sequestration of miR-1183 by lncRNA DDX11-AS1 Drives Gliomagenesis through E2F7 Activation. Oncology research 0 41050080
2025 Novel mechanism of tumor metastasis: DDX11-ATAD5 interaction mediates epithelial-mesenchymal transition to promote gallbladder cancer progression. CytoJournal 0 41664698
2024 LncRNA DDX11-AS1 promotes cell growth, migration and invasion through regulating epithelial-mesenchymal transition in breast cancer. Cellular and molecular biology (Noisy-le-Grand, France) 0 38678629

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