DDX11 is an ATP-dependent DNA helicase associated with nuclear chromatin. Purified human protein unwinds DNA in the 5-prime to 3-prime direction, using accessible single-stranded loading regions and showing substrate-dependent activity on forked duplexes, D-loops and selected G-quadruplexes. DDX11 supports replication under stress and sister-chromatid cohesion, with both catalytic and protein-association contributions under investigation. A nucleolar pool participates in ribosomal chromatin regulation. Pathogenic variants cause Warsaw breakage syndrome.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000785 chromatin | IDA PMID:17105772 The DNA helicase ChlR1 is required for sister chromatid cohe... | ACCEPT | Summary: Chromatin localization in early mitosis. Reason: PMID:17105772 localizes endogenous ChlR1 to prophase/prometaphase chromatin, with loss as metaphase advances. This is stage-dependent chromatin association. |
| GO:0000922 spindle pole | IDA PMID:17105772 The DNA helicase ChlR1 is required for sister chromatid cohe... | KEEP AS NON CORE | Summary: Mitotic spindle-pole localization. Reason: Controlled immunofluorescence in PMID:17105772 supports spindle-pole localization. Localization alone does not establish a spindle-organizing molecular function. |
| GO:0000922 spindle pole | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A supported electronic spindle-pole localization. Reason: The UniProt SL-0448 mapping agrees with the controlled mitotic localization in PMID:17105772. Retain the location without inferring a spindle motor activity. |
| GO:0003676 nucleic acid binding | IEA GO_REF:0000002 | MODIFY | Summary: Refine nucleic-acid binding to experimentally supported DNA and RNA binding. Reason: IPR006555 matches Q96FC9 residues 693–859 and maps nucleic-acid binding. Target DNA mobility-shift assays in PMID:26503245 and controlled CONCR pull-down/RNA immunoprecipitation in PMID:27477908 support DNA and RNA binding, respectively. These binding assertions are distinct from helicase catalysis. Refine the domain-derived descriptor using these target experiments, without treating the domain mapping itself as substrate-specific proof. Proposed replacements: DNA binding RNA binding |
| GO:0003677 DNA binding | IDA PMID:26503245 Tim/Timeless, a member of the replication fork protection co... | ACCEPT | Summary: Direct binding to defined DNA substrates. Reason: PMID:26503245 measures binding of purified human DDX11 to forked DNA, an antiparallel bimolecular G4 and a D-loop by mobility-shift assays. Binding is experimentally distinct from subsequent ATP-driven unwinding. Supporting Evidence: |
| GO:0003677 DNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: DNA binding from a target-matched RAD3-like domain. Reason: IPR010614 matches Q96FC9 residues 231–415 and maps DNA binding. Purified target-protein DNA-binding assays independently support the inference; a broad family name does not establish paralog misassignment. |
| GO:0003678 DNA helicase activity | IBA GO_REF:0000033 | MODIFY | Summary: Refine inherited DNA helicase activity using target directionality. Reason: The PAINT IBD at PTN000158192 is ancestral to target leaf PTN002479319, and the saved PANTHER alignment exactly matches current 970-residue Q96FC9. This is a valid inherited DNA-helicase assertion; target self-evidence and donor count are not objections. The human biochemical directionality experiments in PMID:18499658 justify refinement to 5-prime to 3-prime DNA helicase activity. The refinement comes from target experiments, not a claim that the ancestral node specifies directionality. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000158192 The positive DNA-helicase IBD is ancestral to human target leaf PTN002479319. The broad inherited activity is valid; target biochemical directionality justifies the specific replacement. UniProtKB:Q96FC9 Target experimental evidence is a legitimate descendant source for this IBD. Its presence is not circular propagation. The target alignment matches the 970-residue displayed sequence without assigning historical assays to every product. Proposed replacements: 5'-3' DNA helicase activity |
| GO:0003678 DNA helicase activity | IDA PMID:26503245 Tim/Timeless, a member of the replication fork protection co... | MODIFY | Summary: Refine the assayed DNA helicase activity to its directionality. Reason: PMID:26503245 measures ATP-dependent fork unwinding by purified DDX11 with K50R and nucleotide controls. Together with the directly established 5-prime to 3-prime polarity, this supports the directional term. Proposed replacements: 5'-3' DNA helicase activity |
| GO:0003678 DNA helicase activity | IEA GO_REF:0000002 | MODIFY | Summary: Refine the matched-domain DNA-helicase inference using target biochemistry. Reason: Q96FC9 matches IPR006554, IPR010614 and IPR013020, each carrying the DNA-helicase mapping. The mappings are sound, while human DDX11 directionality experiments in PMID:18499658 support the more specific 5-prime to 3-prime DNA helicase term. Preserve the electronic source and distinguish its broad mapping from the experimental basis for refinement. Proposed replacements: 5'-3' DNA helicase activity |
| GO:0003682 chromatin binding | IDA PMID:26503245 Tim/Timeless, a member of the replication fork protection co... | ACCEPT | Summary: Chromatin association of DDX11 at stressed replication forks. Reason: PMID:26503245 uses cellular chromatin fractions and nuclease-treated co-immunoprecipitation; DDX11 and TIMELESS recruitment increases with hydroxyurea. This supports chromatin association without specifying an origin-recognition sequence. Supporting Evidence: |
| GO:0003682 chromatin binding | IMP PMID:20124417 Human Timeless and Tipin stabilize replication forks and fac... | ACCEPT | Summary: TIMELESS-dependent DDX11 chromatin association. Reason: PMID:20124417 detects DDX11 in chromatin fractions and reduces this pool by TIMELESS depletion. The experiment does not fully separate chromatin recruitment from protein stability, but it supports the existing binding assertion. |
| GO:0003682 chromatin binding | IMP PMID:26089203 The Warsaw breakage syndrome-related protein DDX11 is requir... | KEEP AS NON CORE | Summary: DDX11 association with ribosomal chromatin. Reason: PMID:26089203 ChIP and rDNA pull-down support rDNA association. This nucleolar context is retained separately from the helicase core. |
| GO:0003682 chromatin binding | IMP PMID:27477908 A Long Noncoding RNA Regulates Sister Chromatid Cohesion. | ACCEPT | Summary: CONCR supports chromatin-associated DDX11. Reason: PMID:27477908 shifts DDX11 from chromatin to soluble fractions after CONCR depletion, with FEN1 controls, and detects broad ChIP-seq domains. This supports chromatin association, without assigning direct origin recognition. Supporting Evidence: |
| GO:0003688 DNA replication origin binding | IMP PMID:27477908 A Long Noncoding RNA Regulates Sister Chromatid Cohesion. | MODIFY | Summary: The assayed regions establish chromatin association, not origin-specific binding. Reason: PMID:27477908 reports megabase-scale DDX11 ChIP-seq domains overlapping early-replicating regions, rather than binding to a defined replication-origin sequence. GO:0003688 requires an origin. Chromatin binding preserves the demonstrated association and CONCR dependence. Proposed replacements: chromatin binding |
| GO:0003690 double-stranded DNA binding | IDA PMID:9013641 Characterization of putative human homologues of the yeast c... | ACCEPT | Summary: Double-stranded DNA binding in the original biochemical assay. Reason: PMID:9013641 tests in-vitro-translated hCHLR1 on double-stranded DNA-cellulose with positive and negative protein controls. Retain this measured binding; it does not imply efficient unwinding of blunt duplex DNA. |
| GO:0003697 single-stranded DNA binding | IDA PMID:9013641 Characterization of putative human homologues of the yeast c... | ACCEPT | Summary: Single-stranded DNA binding in the original biochemical assay. Reason: PMID:9013641 tests in-vitro-translated hCHLR1 on single-stranded DNA-cellulose with control proteins. Later purified-protein experiments independently support single-stranded DNA binding and a loading requirement for helicase activity. |
| GO:0003727 single-stranded RNA binding | IDA PMID:27477908 A Long Noncoding RNA Regulates Sister Chromatid Cohesion. | MODIFY | Summary: CONCR association supports RNA binding without a resolved strand preference. Reason: PMID:27477908 uses CONCR capture and reciprocal RNA immunoprecipitation from nuclear extracts. These experiments identify a lncRNA partner but do not compare single- versus double-stranded RNA substrates or resolve the contacted RNA structure. Retain RNA binding without adding an unmeasured strand specificity. Proposed replacements: RNA binding |
| GO:0004386 helicase activity | IDA PMID:10648783 Characterization of the enzymatic activity of hChlR1, a nove... | MODIFY | Summary: DNA and DNA/RNA-hybrid unwinding refine the broad helicase assertion. Reason: Human recombinant hChlR1 shows ATP-dependent DNA displacement with a K50R control. Short-substrate assays support 5-prime to 3-prime DNA unwinding; apparent bidirectionality on a long template is substrate-dependent. Fig. 5B additionally shows displacement of an 18-nt RNA paired with M13 DNA, supporting GO:0033677. The reported co-purifying activity affecting 5-prime labels remains an assay limitation. These experiments do not establish hybrid-specific translocation direction, RNA/RNA unwinding or a native R-loop process. Proposed replacements: 5'-3' DNA helicase activity DNA/RNA helicase activity |
| GO:0004386 helicase activity | IDA PMID:18499658 Studies with the human cohesin establishment factor, ChlR1. ... | MODIFY | Summary: Directional DNA helicase activity refines the broad helicase term. Reason: Purified human hChlR1 expressed in 293 cells unwinds DNA in the 5-prime to 3-prime direction, requires a 5-prime loading region and hydrolysable nucleotide, and loses activity with Walker-A K50R. The more specific directional DNA helicase term describes the directly assayed activity. Proposed replacements: 5'-3' DNA helicase activity |
| GO:0004386 helicase activity | IEA GO_REF:0000002 | MODIFY | Summary: Refine the matched helicase-domain mapping to directional DNA helicase activity. Reason: IPR006555 matches the target helicase C-terminal region and maps helicase activity. Direct human DDX11 biochemistry in PMID:18499658 establishes the more specific 5-prime to 3-prime DNA helicase activity. Preserve the original broad mapping as provenance while using the target experiments for the refinement. Proposed replacements: 5'-3' DNA helicase activity |
| GO:0004386 helicase activity | TAS PMID:8798685 The human homologue of the yeast CHL1 gene is a novel kerati... | MODIFY | Summary: Refine the historical helicase prediction using subsequent human biochemistry. Reason: PMID:8798685 identified a keratinocyte growth-factor-responsive cDNA and inferred a helicase from its sequence; it did not assay helicase activity. Subsequent human experiments in PMID:10648783 and PMID:18499658 establish 5-prime to 3-prime DNA helicase activity. Preserve the original TAS provenance and make the additional experimental basis for the refinement explicit. Proposed replacements: 5'-3' DNA helicase activity |
| GO:0005515 protein binding | IPI PMID:17105772 The DNA helicase ChlR1 is required for sister chromatid cohe... | KEEP AS NON CORE | Summary: Association with the RAD21-containing cohesin complex. Reason: PMID:17105772 supports endogenous RAD21 co-immunoprecipitation with depletion controls. Direct binary binding is unresolved; retain the complex association without assigning RAD21 structural activity to DDX11. |
| GO:0005515 protein binding | IPI PMID:17105772 The DNA helicase ChlR1 is required for sister chromatid cohe... | KEEP AS NON CORE | Summary: Association with cohesin subunit SMC3. Reason: PMID:17105772 detects SMC3 in DDX11 immunoprecipitates but explicitly leaves direct binding unresolved. SMC3 catalytic properties do not justify enzyme-binding refinement of this complex association. |
| GO:0005515 protein binding | IPI PMID:17189189 ChlR1 is required for loading papillomavirus E2 onto mitotic... | UNDECIDED | Summary: E2 association is reported, but the detailed original assay remains inaccessible. Reason: The PMID:17189189 abstract reports ChlR1–papillomavirus E2 binding and an E2 W130R defect. Publisher and repository attempts did not recover the original Methods/Results. Preserve the source assertion as undecided pending assay-level verification; do not infer a specific host transcriptional function or deny the interaction. |
| GO:0005515 protein binding | IPI PMID:18499658 Studies with the human cohesin establishment factor, ChlR1. ... | KEEP AS NON CORE | Summary: PCNA association under the original assay conditions. Reason: The original Fig. 6E shows reciprocal immunoprecipitation from 293-cell lysates supplemented with recombinant HA-PCNA; purified-protein association is also reported as data not shown. Retain the PCNA association without representing the spiked-lysate result as an endogenous native complex or assigning PCNA clamp activity to DDX11. This generic association is not a standalone core molecular function. |
| GO:0005515 protein binding | IPI PMID:18499658 Studies with the human cohesin establishment factor, ChlR1. ... | KEEP AS NON CORE | Summary: RFC2 association within an alternative clamp-loader context. Reason: The original Fig. 6A detects endogenous p37/RFC2 in hChlR1 immunoprecipitates; the official P35250 record identifies RFC2. The authors explicitly caution that associations with individual Ctf18-RFC subunits likely include other complex components. Preserve the association without converting it to proven direct binary enzyme binding or clamp-loader catalytic activity. |
| GO:0005515 protein binding | IPI PMID:18499658 Studies with the human cohesin establishment factor, ChlR1. ... | MODIFY | Summary: Direct binding to the nuclease FEN1. Reason: The original Fig. 7A-C reports controlled reciprocal cellular co-immunoprecipitation and binding of isolated recombinant FEN1 and hChlR1. FEN1 is the catalytic nuclease partner, supporting enzyme binding. FEN1 cleavage stimulation occurs at high hChlR1:FEN1 ratios and does not require hChlR1 ATPase/helicase activity; it does not give DDX11 endonuclease activity or establish its physiological mechanism. Proposed replacements: enzyme binding |
| GO:0005515 protein binding | IPI PMID:18499658 Studies with the human cohesin establishment factor, ChlR1. ... | KEEP AS NON CORE | Summary: DCC1 association in cellular co-immunoprecipitation. Reason: DCC1 and hChlR1 co-immunoprecipitate in reciprocal tagged 293-cell experiments in Fig. 6A/C. The original paper warns that other Ctf18-RFC components can mediate individual-subunit associations. Retain the observed complex association without claiming purified direct binary DCC1 binding, a DCC1 enzymatic function, or constitutive DDX11 membership of the clamp loader. |
| GO:0005515 protein binding | IPI PMID:18499658 Studies with the human cohesin establishment factor, ChlR1. ... | KEEP AS NON CORE | Summary: CTF8 association reported by the original study. Reason: The original reports reciprocal hChlR1-Ctf8 immunoprecipitation using Ctf8 antisera as data not shown. As for DCC1 and RFC2, the authors explicitly allow association through the Ctf18-RFC complex. Retain the curator-backed association as non-core; absence of a displayed figure is not contradictory evidence or a reason to remove it. |
| GO:0005515 protein binding | IPI PMID:20124417 Human Timeless and Tipin stabilize replication forks and fac... | KEEP AS NON CORE | Summary: TIMELESS association in a replication/cohesion context. Reason: PMID:20124417 shows reciprocal tagged-protein co-immunoprecipitation of endogenous partners; the authors report persistence after DNase treatment. TIMELESS is a replication-fork regulator, and this pair does not establish a distinct DDX11 adaptor activity. |
| GO:0005515 protein binding | IPI PMID:26089203 The Warsaw breakage syndrome-related protein DDX11 is requir... | MODIFY | Summary: Association with the RNA polymerase I machinery. Reason: PMID:26089203 co-immunoprecipitates POLR1A. Its verified polymerase identity supports RNA polymerase binding, without claiming purified binary binding. Proposed replacements: RNA polymerase binding |
| GO:0005515 protein binding | IPI PMID:26089203 The Warsaw breakage syndrome-related protein DDX11 is requir... | MODIFY | Summary: Association with the DNA-binding transcription factor UBTF. Reason: PMID:26089203 co-immunoprecipitates UBTF, an rDNA-binding transcription factor. Refine the partner class without assigning transcription-factor activity to DDX11. Proposed replacements: DNA-binding transcription factor binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: FUZ-associated DDX11 in BioPlex affinity proteomics. Reason: The PMID:33961781 original describes tagged-bait AP-MS and gene-level aggregation. The saved IntAct record identifies FUZ bait and DDX11 prey in human HEK293 cells (EBI-54746188; spoke-expanded association). Retain the association without claiming direct binding, native stoichiometry, an isoform, or a ciliary DDX11 function. |
| GO:0005515 protein binding | IPI PMID:34819669 A multi-scale map of cell structure fusing protein images an... | UNDECIDED | Summary: The second FUZ-associated source requires pair-level verification. Reason: PMID:34819669 combines imaging and AP-MS, including new affinity experiments. Its original Methods were read, but the exact FUZ–DDX11 supplementary record was not recovered; attempted supplementary downloads returned challenges or errors, and the targeted current IntAct query returned no records. The independently supported PMID:33961781 pair is retained separately. This is an unresolved source-specific assertion, not evidence against the interaction. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding from matched ATPase domains and direct assays. Reason: IPR006555, IPR010614 and IPR014013 match Q96FC9 and carry ATP-binding mappings. PMID:22102414 independently measures ATP binding, distinguishing nucleotide binding from productive hydrolysis in K897del and K50R mutants. |
| GO:0005634 nucleus | EXP PMID:17105772 The DNA helicase ChlR1 is required for sister chromatid cohe... | ACCEPT | Summary: Nuclear DDX11 in interphase. Reason: PMID:17105772 supports interphase nuclear localization with antibody and depletion controls. The antibody evidence does not establish equal localization of every current splice product. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Inherited nuclear localization on the DDX11/Chl1 branch. Reason: The target is a descendant of PAINT node PTN000158371, which carries the nuclear IBD. Saved tree and alignment identify the target correctly; human localization provides independent support. The target appearing among the descendant evidence is expected, not circular. |
| GO:0005634 nucleus | IDA PMID:17189189 ChlR1 is required for loading papillomavirus E2 onto mitotic... | ACCEPT | Summary: Nuclear localization is independently established. Reason: Although the full PMID:17189189 viral study could not be recovered, nuclear localization is directly supported by PMID:17105772 and current HPA immunofluorescence. Retain this clearly correct location without claiming that the inaccessible viral Methods were read. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt nuclear localization agrees with primary evidence. Reason: The SL-0191 nuclear mapping is explicitly present in the frozen UniProt record and is supported by human immunofluorescence in PMID:17105772. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: HPA supports nucleoplasmic localization. Reason: The saved HPA v25 DDX11 record reports enhanced nucleoplasmic localization with supported antibody HPA065197 in HEK293, HeLa and U2OS cells. This is gene-level antibody evidence, not a demonstration for all five splice products. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1791116 | ACCEPT | Summary: Reactome explicitly places the DDX11 product in nucleoplasm. Reason: R-HSA-1791116 outputs physical entity R-HSA-535492, whose reference protein is Q96FC9 and whose compartment is GO:0005654. This supports the location; DDX11 being an expression product does not make it a catalyst of its own expression. |
| GO:0005694 chromosome | EXP PMID:17189189 ChlR1 is required for loading papillomavirus E2 onto mitotic... | KEEP AS NON CORE | Summary: Chromosome association has independent stage-specific support. Reason: The original PMID:17189189 Methods were unavailable. PMID:17105772 independently places DDX11 on early-mitotic chromatin and shows its later release. Retain the broad chromosome association without asserting persistent mitotic tethering to viral E2. |
| GO:0005694 chromosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic chromosome localization is compatible with the primary data. Reason: The UniProt SL-0468 mapping is explicitly present. Independent human evidence shows stage-dependent chromatin association; the location is not an assertion that DDX11 is a permanent structural chromosome component. |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: HPA supports a nucleolar DDX11 pool. Reason: The current HPA record reports additional nucleolar localization in HeLa and U2OS with HPA065197, alongside nucleoplasm. Retain the compartmental pool without implying identical localization of every splice product. |
| GO:0005730 nucleolus | IDA PMID:26089203 The Warsaw breakage syndrome-related protein DDX11 is requir... | KEEP AS NON CORE | Summary: Nucleolar localization has independent 2015 evidence. Reason: PMID:26089203 reports nucleolin colocalization and isolated nucleolar fractions in human cells. Retain this compartmental pool. |
| GO:0005730 nucleolus | IDA PMID:9013641 Characterization of putative human homologues of the yeast c... | KEEP AS NON CORE | Summary: Historical nucleolar staining needs its antibody caveat. Reason: PMID:9013641 reports nucleolar staining and fractionation. PMID:17105772 later found that early Hel1 bleeds differed from affinity-purified material. Independent 2015 and HPA evidence support a nucleolar pool, without resolving the historical reagent discrepancy. |
| GO:0005730 nucleolus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The nucleolar mapping is supported beyond the historical reagent. Reason: UniProt SL-0188 agrees with current HPA metadata and the independently read PMID:26089203 localization experiments. The earlier Hel1 antibody discrepancy is retained in the evidence notes, not generalized into absence from nucleoli. |
| GO:0005813 centrosome | IDA PMID:17105772 The DNA helicase ChlR1 is required for sister chromatid cohe... | KEEP AS NON CORE | Summary: Centrosomal localization in mitotic cells. Reason: PMID:17105772 uses gamma-tubulin colocalization to identify centrosomal poles. Retain the localization without inferring a separate centrosome-assembly function. |
| GO:0005813 centrosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic centrosome localization has direct support. Reason: The SL-0048 mapping agrees with gamma-tubulin colocalization in PMID:17105772. It does not establish an independent centrosomal molecular activity. |
| GO:0006974 DNA damage response | IMP PMID:23797032 Roles of ChlR1 DNA helicase in replication recovery from DNA... | ACCEPT | Summary: DDX11 contributes to the cellular DNA-damage response. Reason: PMID:23797032 shows persistent damage markers, reduced survival after cisplatin and delayed repair/recovery after DDX11 depletion. These support the broad response assertion; the study does not fully separate repair effects from cohesion defects. Supporting Evidence: |
| GO:0007062 sister chromatid cohesion | IDA PMID:17105772 The DNA helicase ChlR1 is required for sister chromatid cohe... | ACCEPT | Summary: A central role in sister-chromatid cohesion. Reason: PMID:17105772 depletion experiments widen sister-chromatid spacing and disrupt chromosome segregation. Retain the process without treating DDX11 as a structural cohesin subunit. |
| GO:0008094 ATP-dependent activity, acting on DNA | IDA PMID:10648783 Characterization of the enzymatic activity of hChlR1, a nove... | MODIFY | Summary: Refine ATP-driven DNA activity to DNA and DNA/RNA-hybrid unwinding. Reason: PMID:10648783 demonstrates ATP-driven DNA strand displacement and a positive RNA/DNA-hybrid assay (Fig. 5B). Preserve both substrate capabilities through the proposed replacements. The directionality refinement applies to DNA assays; the hybrid result retains the preparation limitation detailed in the helicase-row review. Proposed replacements: 5'-3' DNA helicase activity DNA/RNA helicase activity |
| GO:0008094 ATP-dependent activity, acting on DNA | IDA PMID:26503245 Tim/Timeless, a member of the replication fork protection co... | MODIFY | Summary: Refine ATP-driven DNA activity to the assayed helicase. Reason: PMID:26503245 demonstrates ATP-dependent DNA strand displacement with mutant and nucleotide controls. Established directional specificity supports the more informative 5-prime to 3-prime DNA-helicase term. Proposed replacements: 5'-3' DNA helicase activity |
| GO:0008094 ATP-dependent activity, acting on DNA | IMP PMID:26089203 The Warsaw breakage syndrome-related protein DDX11 is requir... | MODIFY | Summary: Retain the measured rDNA-associated ATP hydrolysis without inferring coupling. Reason: PMID:26089203 purifies FLAG-tagged human DDX11 and mutant proteins from HEK293 cells, then measures ATPase activity with an rDNA promoter fragment. This directly supports ATP hydrolysis and reduced activity of the tested mutants. GO:0008094 requires catalytic modification of DNA driven by ATP hydrolysis; the reported turnover assay does not measure that coupled reaction. Refine this source-specific assertion to GO:0016887, retaining its rDNA context without claiming directional rDNA unwinding. Proposed replacements: ATP hydrolysis activity |
| GO:0008186 ATP-dependent activity, acting on RNA | IDA PMID:27477908 A Long Noncoding RNA Regulates Sister Chromatid Cohesion. | MODIFY | Summary: Retain CONCR-stimulated ATP hydrolysis without an unmeasured coupled reaction. Reason: PMID:27477908 measures greater ATP hydrolysis with CONCR than with a matched control RNA in time-course and RNA-titration experiments. GO:0008186 requires RNA-dependent ATP hydrolysis that drives another reaction; its RNA-dependent ATPase synonym does not remove that requirement. The assay establishes RNA-stimulated turnover but does not identify the coupled reaction, so GO:0016887 captures the demonstrated chemistry. Cellular rescue by wild-type but not K50R DDX11 supports catalytic involvement in cohesion without demonstrating biochemical coupling to an RNA reaction. Proposed replacements: ATP hydrolysis activity |
| GO:0016818 hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides | IEA GO_REF:0000002 | MODIFY | Summary: Refine the broad phosphorus-anhydride hydrolase mapping to ATP hydrolysis. Reason: IPR006554 and IPR006555 match the target and carry the broad phosphorus-anhydride hydrolase mapping. Direct ATP-turnover experiments with human DDX11 in PMID:18499658 identify ATP as the hydrolyzed substrate and support GO:0016887. This chemistry refinement does not create another catalytic core. Proposed replacements: ATP hydrolysis activity |
| GO:0016887 ATP hydrolysis activity | EXP PMID:10648783 Characterization of the enzymatic activity of hChlR1, a nove... | ACCEPT | Summary: DNA-stimulated ATP hydrolysis by recombinant human ChlR1. Reason: The original directly measures DNA-stimulated ATP hydrolysis by recombinant human hChlR1, with Walker-A K50R at background levels. ATP hydrolysis is the experimentally measured energy-supplying reaction of the helicase. The current GO definition explicitly retains this ATPase reaction alongside an ATP-driven overall function; the core will use the directional helicase term once. |
| GO:0016887 ATP hydrolysis activity | EXP PMID:18499658 Studies with the human cohesin establishment factor, ChlR1. ... | ACCEPT | Summary: ATP hydrolysis by purified human ChlR1. Reason: The original directly measures ATP hydrolysis by purified 293-cell-derived hChlR1, stimulated by single-stranded DNA and strongly impaired by K50R. ATP is hydrolysed much more efficiently than dATP. Preserve this measured chemical reaction; it supports, but is not a separate core from, ATP-driven DNA unwinding. |
| GO:0016887 ATP hydrolysis activity | EXP PMID:22102414 Biochemical characterization of Warsaw breakage syndrome hel... | ACCEPT | Summary: ATP hydrolysis distinguished from ATP binding in mutant analyses. Reason: Original ATPase assays use radiolabelled ATP and M13 ssDNA with WT, K50R and patient K897del controls. WT shows DNA-dependent ATP turnover whereas both mutants have very low activity; retained ATP binding by K897del is distinguished from productive hydrolysis. Accept the directly measured ATP-hydrolysis activity without extrapolating it across all splice products. |
| GO:0016887 ATP hydrolysis activity | EXP PMID:26089203 The Warsaw breakage syndrome-related protein DDX11 is requir... | ACCEPT | Summary: ATP hydrolysis is directly measured in the rDNA study. Reason: PMID:26089203 measures ATP turnover with purified tagged protein and rDNA, including activity-defective mutants. This supports the ATPase reaction. |
| GO:0016887 ATP hydrolysis activity | EXP PMID:27477908 A Long Noncoding RNA Regulates Sister Chromatid Cohesion. | ACCEPT | Summary: CONCR-stimulated ATP hydrolysis is directly measured. Reason: PMID:27477908 uses time courses and RNA titrations to measure ATP turnover by purified DDX11, comparing CONCR with control RNA. Accept the chemical reaction while leaving the RNA-dependent coupled activity unresolved. Supporting Evidence: |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000116 | ACCEPT | Summary: The Rhea mapping describes the experimentally measured chemistry. Reason: RHEA:13065 is ATP + water to ADP, phosphate and proton. The frozen UniProt catalytic annotation and the official Rhea equation agree with direct human DDX11 ATPase assays. |
| GO:0030496 midbody | IDA PMID:17105772 The DNA helicase ChlR1 is required for sister chromatid cohe... | KEEP AS NON CORE | Summary: Late-mitotic midbody localization. Reason: PMID:17105772 colocalizes ChlR1 with a midbody marker. The authors leave its function there unresolved; retain localization alone. |
| GO:0030496 midbody | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic midbody localization has direct support. Reason: UniProt SL-0469 is supported by the late-mitotic imaging in PMID:17105772; a cytokinesis mechanism is not established. |
| GO:0030892 mitotic cohesin complex | IDA NOT PMID:17105772 The DNA helicase ChlR1 is required for sister chromatid cohe... | KEEP AS NON CORE | Summary: Retain the negated assertion in its metaphase context. Reason: PMID:17105772 reports absent centromeric ChlR1 at metaphase where cohesin remains. This supports the source NOT assertion in that context, without denying earlier association with cohesin or equating association with structural membership. |
| GO:0031297 replication fork processing | IMP PMID:26503245 Tim/Timeless, a member of the replication fork protection co... | ACCEPT | Summary: DDX11 supports stalled-fork processing and recovery. Reason: PMID:26503245 uses DNA-fiber assays after hydroxyurea, DDX11/TIMELESS depletion and chromatin recruitment experiments. Retain the existing fork-processing assertion, while distinguishing the cellular recovery phenotype from a fully resolved biochemical fork intermediate. Supporting Evidence: |
| GO:0032091 negative regulation of protein binding | IMP PMID:26089203 The Warsaw breakage syndrome-related protein DDX11 is requir... | KEEP AS NON CORE | Summary: A secondary effect on UBF–HDAC1 association. Reason: PMID:26089203 depletion increases UBF–HDAC1 co-immunoprecipitation. Retain negative regulation of binding without claiming direct disruption by DDX11. |
| GO:0034085 establishment of sister chromatid cohesion | IBA GO_REF:0000033 | ACCEPT | Summary: Inherited establishment of sister-chromatid cohesion. Reason: The target and budding-yeast Chl1 donor descend from PTN000158371. Current QuickGO retains the donor IMP assertion from PMID:23334284, and the PAINT IBD is experimentally grounded. Human cohesion evidence agrees. One donor is not weak support; this is a clade-level inherited assertion. |
| GO:0035563 positive regulation of chromatin binding | IDA PMID:26089203 The Warsaw breakage syndrome-related protein DDX11 is requir... | KEEP AS NON CORE | Summary: DDX11 promotes UBF recruitment to rDNA. Reason: PMID:26089203 ChIP after depletion supports reduced UBF recruitment. Retain the regulatory outcome without assuming a direct chromatin-loading mechanism. |
| GO:0043139 5'-3' DNA helicase activity | EXP PMID:10648783 Characterization of the enzymatic activity of hChlR1, a nove... | ACCEPT | Summary: Positive 5-prime to 3-prime DNA unwinding with historical substrate caveats. Reason: The original demonstrates preferential 5-prime to 3-prime strand displacement on short substrates. Its long-template apparent bidirectionality is recorded as an assay-dependent historical result, while the later 2008 human study establishes exclusively 5-prime to 3-prime translocation under its defined conditions. The positive directional assertion is supported; no reverse-direction core is added. |
| GO:0043139 5'-3' DNA helicase activity | EXP PMID:22102414 Biochemical characterization of Warsaw breakage syndrome hel... | ACCEPT | Summary: Directional DNA unwinding by wild-type human ChlR1. Reason: Purified human WT hChlR1 unwinds 5-prime-tailed and forked duplexes, 5-prime flaps and a tailed D-loop in ATP-dependent assays; K50R and K897del are defective. The strand-loading requirements and substrate geometry support 5-prime to 3-prime DNA helicase activity. Strong activity on one two-stranded antiparallel G4 model is not generalized to all G4 structures or genomic sites. |
| GO:0043139 5'-3' DNA helicase activity | IDA PMID:18499658 Studies with the human cohesin establishment factor, ChlR1. ... | ACCEPT | Summary: Directly established 5-prime to 3-prime DNA helicase activity. Reason: The original directly demonstrates 5-prime to 3-prime DNA translocation and ATP-dependent duplex unwinding using purified human hChlR1, defined polarity substrates and K50R controls. RPA and Ctf18-RFC extend unwinding of longer duplexes. The directional DNA helicase activity is a central molecular function. |
| GO:0043139 5'-3' DNA helicase activity | IEA GO_REF:0000003 | ACCEPT | Summary: The enzyme-class mapping matches directional helicase chemistry. Reason: Official EC 5.6.2.3 denotes ATP-coupled 5-prime to 3-prime DNA helicase activity. Its UniProt mapping agrees with the directly read human helicase experiments. |
| GO:0045142 triplex DNA binding | IDA PMID:26503245 Tim/Timeless, a member of the replication fork protection co... | MODIFY | Summary: The assayed three-stranded substrate is a D-loop, not a DNA triple helix. Reason: PMID:26503245 measures binding to a D-loop formed by an invading strand paired with one duplex strand. GO:0045142 instead means a DNA triple helix. GO:0062037 matches the actual assayed substrate and preserves the positive binding result. Proposed replacements: D-loop DNA binding |
| GO:0045876 positive regulation of sister chromatid cohesion | IMP PMID:18499658 Studies with the human cohesin establishment factor, ChlR1. ... | ACCEPT | Summary: Positive regulation of sister-chromatid cohesion in human cells. Reason: In HeLa cells, hChlR1 siRNA produces premature sister-chromatid separation, assessed by metaphase spreads and chromosome-9 centromeric FISH; control siRNA and SCC1 depletion provide comparisons. This supports the existing positive regulation of cohesion assertion. It does not by itself identify the molecular step or establish that ATPase activity is required for every cohesion phenotype. |
| GO:0045876 positive regulation of sister chromatid cohesion | IMP PMID:20124417 Human Timeless and Tipin stabilize replication forks and fac... | ACCEPT | Summary: DDX11 supports sister-chromatid cohesion in the TIMELESS pathway. Reason: PMID:20124417 shows cohesion defects after DDX11 depletion and rescue of Tipin-depletion defects by DDX11 overexpression. The TIMELESS-depletion rescue was weaker and not statistically significant in that comparison; it is not described as complete rescue. |
| GO:0045876 positive regulation of sister chromatid cohesion | IMP PMID:27477908 A Long Noncoding RNA Regulates Sister Chromatid Cohesion. | ACCEPT | Summary: Wild-type DDX11 rescues CONCR-associated cohesion defects. Reason: PMID:27477908 reports rescue by wild-type DDX11 but not ATPase-defective K50R in CONCR-depleted cells. This supports positive regulation of cohesion in the tested context without establishing that every DDX11 contribution uses the same catalytic mechanism. Supporting Evidence: |
| GO:0051880 G-quadruplex DNA binding | IDA PMID:26503245 Tim/Timeless, a member of the replication fork protection co... | ACCEPT | Summary: Direct binding to an antiparallel bimolecular G4 substrate. Reason: PMID:26503245 measures purified DDX11 binding to the tested G4 structure and enhancement by TIMELESS. Retain G-quadruplex binding without extending the result to all G4 topologies or physiological genomic sites. Supporting Evidence: |
| GO:0070062 extracellular exosome | HDA PMID:18570454 Proteomic analysis of exosomes from human neural stem cells ... | UNDECIDED | Summary: The exosome protein-level detection remains unverified. Reason: PMID:18570454 describes size-fractionated neural-stem-cell exosomes and LC-MS/MS, but its accessible abstract does not identify DDX11. Original supplementary protein evidence was not recovered. Keep this HDA assertion undecided; do not infer contamination or reject the curator from the nuclear helicase function alone. |
| GO:0072711 cellular response to hydroxyurea | IMP PMID:23797032 Roles of ChlR1 DNA helicase in replication recovery from DNA... | KEEP AS NON CORE | Summary: Hydroxyurea-associated replication recovery is supported with a protocol caveat. Reason: In PMID:23797032 hydroxyurea synchronizes cells before cisplatin and EdU-recovery assays, so it is not an isolated hydroxyurea-response test. Independent PMID:26503245 hydroxyurea fork-restart experiments support the broad response; retain it as non-core. |
| GO:0072711 cellular response to hydroxyurea | IMP PMID:26503245 Tim/Timeless, a member of the replication fork protection co... | KEEP AS NON CORE | Summary: Response to hydroxyurea-induced replication stress. Reason: PMID:26503245 directly tests DNA-fiber progression and restart after hydroxyurea in DDX11-depleted cells. Retain the chemical-response label as a context of the more informative fork-processing activity. |
| GO:0072719 cellular response to cisplatin | IMP PMID:23797032 Roles of ChlR1 DNA helicase in replication recovery from DNA... | KEEP AS NON CORE | Summary: Cisplatin sensitivity and delayed recovery after DDX11 depletion. Reason: PMID:23797032 reports reduced clonogenic survival and persistent damage markers after cisplatin. Retain this response without assigning direct platinum-lesion recognition or a drug-metabolizing activity. |
| GO:0160225 G-quadruplex unwinding activity | IDA PMID:26503245 Tim/Timeless, a member of the replication fork protection co... | ACCEPT | Summary: Unwinding of the tested G4 DNA structure. Reason: PMID:26503245 demonstrates ATP-dependent unwinding of an antiparallel bimolecular G4 by purified DDX11, enhanced by TIMELESS. This existing activity assertion describes the directly performed DNA-remodelling step; it does not establish universal G4 activity or genomic targeting. Supporting Evidence: |
| GO:1901838 positive regulation of transcription of nucleolar large rRNA by RNA polymerase I | IMP PMID:26089203 The Warsaw breakage syndrome-related protein DDX11 is requir... | KEEP AS NON CORE | Summary: A supported rRNA-transcription phenotype. Reason: PMID:26089203 depletion lowers pre-rRNA and reporter output. Retain the positive regulatory process separately from the primary helicase core. |
| GO:1904976 cellular response to bleomycin | IMP PMID:23797032 Roles of ChlR1 DNA helicase in replication recovery from DNA... | KEEP AS NON CORE | Summary: Bleomycin-associated DNA-damage response. Reason: PMID:23797032 reports persistent damage after bleomycin in DDX11-depleted cells. Retain the tested response context without inferring a direct bleomycin-binding or detoxification activity. |
| GO:1990700 nucleolar chromatin organization | IMP PMID:26089203 The Warsaw breakage syndrome-related protein DDX11 is requir... | KEEP AS NON CORE | Summary: DDX11 influences nucleolar chromatin state. Reason: PMID:26089203 reports altered rDNA chromatin marks after depletion. Retain this downstream organization phenotype without assigning a histone-modifying enzyme activity. |
| GO:2000781 positive regulation of double-strand break repair | IMP PMID:23797032 Roles of ChlR1 DNA helicase in replication recovery from DNA... | KEEP AS NON CORE | Summary: DDX11 supports efficient double-strand-break repair. Reason: PMID:23797032 follows an induced I-PpoI break and DNA-damage markers after depletion. Repair is delayed, supporting the regulatory assertion. The authors explicitly cannot exclude secondary effects of cohesion defects; a direct DDX11 repair reaction is not established here. |
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Download this section (compressed HTML)Q: Which DDX11 splice products are present in the nuclear and nucleolar pools, and which retain the measured helicase activity? Historical constructs and antibody epitopes do not establish equivalence across all five products.
Q: Does CONCR-stimulated ATP hydrolysis drive a specific RNA-dependent reaction, and are the broad CONCR-dependent chromatin domains associated with defined replication origins?
Q: Which physiological contributions of DDX11 to cohesion depend on helicase catalysis, and which depend on protein associations such as FEN1 or the replisome?
Q: Which physiological substrates, if any, correspond to the DNA/RNA-hybrid unwinding capacity measured with short RNA oligonucleotides on DNA loading strands? The historical assays do not establish RNA/RNA unwinding or a native R-loop-processing role.
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