ddb-1

UniProt ID: Q21554
Organism: Caenorhabditis elegans
Review Status: COMPLETE
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Gene Description

DDB-1 is the C. elegans ortholog of DNA damage-binding protein 1, a large triple beta-propeller adaptor of CRL4 (cullin-4-RING) E3 ubiquitin ligases. DDB-1 binds CUL-4 specifically among the worm cullins and recruits DCAF substrate receptors, linking them to the cullin scaffold. The CUL-4/DDB-1 complex associates with and degrades the replication-licensing factor CDT-1 during S phase, preventing DNA re-replication in proliferating larval blast cells; with CDT-2 it targets the translesion polymerase POLH-1 during the embryonic DNA damage response, and with the DCAF WDR-23 it represses the stress-responsive transcription factor SKN-1. DDB-1 is broadly expressed in proliferating larval cells and at high levels in the adult spermatheca, and is predicted to act in the nucleus and cytoplasm.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0003676 nucleic acid binding
IEA
GO_REF:0000002 		REMOVE
Summary: InterPro (CPSF_A domain) mapping to nucleic acid binding.
Reason: The CPSF_A beta-propeller domain is shared with RNA-processing CPSF1 proteins; DDB1 family proteins act as protein adaptors of CRL4 ligases, and damaged-DNA binding in the DDB complex is provided by DDB2, not DDB1. No worm evidence for nucleic acid binding exists. Consistent with the human DDB1 review.
GO:0005515 protein binding
IPI
PMID:17145765
The Caenorhabditis elegans replication licensing factor CDT-... 		MODIFY
Summary: Interaction of DDB-1 with the substrate CDT-1 (and, in the same study, with CUL-4).
Reason: Protein binding is uninformative. The paper shows DDB-1 binding both CUL-4 and the CRL4 substrate CDT-1, consistent with the bridging (scaffold/adaptor) role of DDB1 in CRL4 ligases.
Supporting Evidence:
PMID:17145765
DDB-1 interacts specifically with CUL-4, but not with other cullins, in the yeast two-hybrid assay
PMID:17145765
DDB-1 physically associates with CDT-1, indicating that CDT-1 is a direct substrate of the CUL-4/DDB-1 complex.
GO:0005515 protein binding
IPI
PMID:19273594
The WD40 repeat protein WDR-23 functions with the CUL4/DDB1 ... 		MODIFY
Summary: Interaction of DDB-1 with the DCAF WDR-23 (P90794).
Reason: Binding the WD40 DCAF WDR-23 and linking it to CUL-4 is the canonical DDB1 bridging activity; protein binding is uninformative. Abstract-only cache, but the abstract states the WDR-23 interaction with CUL-4/DDB-1.
Supporting Evidence:
PMID:19273594
SKN-1 protein levels, nuclear accumulation, and activity are repressed by the WD40 repeat protein WDR-23, which interacts with the CUL-4/DDB-1 ubiquitin ligase to presumably target the transcription factor for proteasomal degradation.
GO:0005515 protein binding
IPI
PMID:19273594
The WD40 repeat protein WDR-23 functions with the CUL4/DDB1 ... 		MODIFY
Summary: Interaction of DDB-1 with WDR-23 (WormBase gene identifier form).
Reason: Same interaction as the P90794 row; replace with the scaffold activity term.
Supporting Evidence:
PMID:19273594
SKN-1 protein levels, nuclear accumulation, and activity are repressed by the WD40 repeat protein WDR-23, which interacts with the CUL-4/DDB-1 ubiquitin ligase to presumably target the transcription factor for proteasomal degradation.
GO:0005634 nucleus
IBA
GO_REF:0000033 		ACCEPT
Summary: IBA placing DDB-1 in the nucleus.
Reason: Nuclear substrates (CDT-1, POLH-1, SKN-1) and conservation across the DDB1 clade.
Supporting Evidence:
file:worm/ddb-1/ddb-1-uniprot.txt
Promotes the degradation of the replication licensing factor cdt-1 during S-phase, thereby preventing rereplication of DNA during a single round of cell division.
GO:0005634 nucleus
IEA
GO_REF:0000120 		ACCEPT
Summary: Automated nucleus annotation.
Reason: Duplicates the accepted IBA.
Supporting Evidence:
file:worm/ddb-1/ddb-1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
GO:0005634 nucleus
ISS
GO_REF:0000024 		ACCEPT
Summary: ISS nucleus annotation from human DDB1 (Q16531).
Reason: Consistent with the IBA and with nuclear CRL4 substrates.
Supporting Evidence:
file:worm/ddb-1/ddb-1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
GO:0005737 cytoplasm
IEA
GO_REF:0000044 		ACCEPT
Summary: UniProt subcellular-location mapping to cytoplasm.
Reason: DDB1 is nucleocytoplasmic in other species; reasonable, non-core location.
Supporting Evidence:
file:worm/ddb-1/ddb-1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
GO:0005737 cytoplasm
ISS
GO_REF:0000024 		ACCEPT
Summary: ISS cytoplasm annotation from human DDB1.
Reason: As above.
Supporting Evidence:
file:worm/ddb-1/ddb-1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
GO:0006281 DNA repair
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: IBA to DNA repair, from human DDB1 and S. pombe Ddb1.
Reason: DDB1 participates in nucleotide excision repair via CRL4-DDB2 in other species and UniProt carries this by similarity. Worm-specific repair data are lacking; the worm evidence instead concerns licensing-factor and POLH-1 degradation.
Supporting Evidence:
file:worm/ddb-1/ddb-1-uniprot.txt
Plays a role in DNA repair.
GO:0016567 protein ubiquitination
IEA
GO_REF:0000041 		ACCEPT
Summary: UniPathway mapping to protein ubiquitination.
Reason: DDB-1 is a core CRL4 subunit required for CDT-1 degradation.
Supporting Evidence:
PMID:17145765
The CUL-4/DDB-1 complex is required for CDT-1 degradation during S phase and for restraining DNA rereplication.
GO:0035861 site of double-strand break
IBA
GO_REF:0000033 		MARK AS OVER ANNOTATED
Summary: IBA to site of double-strand break, seeded from S. pombe Ddb1.
Reason: No worm evidence places DDB-1 at double-strand breaks; the known worm CRL4 roles are S-phase licensing control and POLH-1 turnover. Matches the human DDB1 review's treatment.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
Sources checked:
PANTHER:PTN000068364 SUPPORTS SOURCE BUT NOT TARGET
Experimental support at this node comes from S. pombe Ddb1 at double-strand breaks; no worm evidence places DDB-1 at DSB sites, and its worm roles are replication-licensing control.
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
IBA
GO_REF:0000033 		ACCEPT
Summary: IBA to proteasome-mediated ubiquitin-dependent protein catabolism.
Reason: Supported by worm experimental data (CDT-1 and POLH-1 degradation).
Supporting Evidence:
PMID:17145765
DDB-1 is required for CDT-1 degradation during S phase.
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
IGI
PMID:19111656
Regulated proteolysis of DNA polymerase eta during the DNA-d... 		ACCEPT
Summary: ddb-1 co-depletion stabilised POLH-1 in MMS-treated gei-17(RNAi) embryos.
Reason: Direct worm genetic evidence for CRL4-dependent proteolysis.
Supporting Evidence:
PMID:19111656
Co-depletion of pcn-1 stabilized POLH-1 in MMS-exposed gei-17 RNAi embryos (Figure 2B), as did co-depletion of cul-4, ddb-1, and cdt-2 (Figure 2C).
GO:0080008 Cul4-RING E3 ubiquitin ligase complex
IPI
PMID:17145765
The Caenorhabditis elegans replication licensing factor CDT-... 		NEW
Summary: DDB-1 binds CUL-4 specifically and functions with it as the CUL-4/DDB-1 complex that degrades CDT-1.
Reason: Worm CUL-4 carries this complex term (IBA) and human DDB1 is a defining member; worm DDB-1 lacks any complex annotation despite direct evidence.
Supporting Evidence:
PMID:17145765
DDB-1 interacts specifically with CUL-4, but not with other cullins, in the yeast two-hybrid assay
PMID:17145765
The CUL-4/DDB-1 complex is required for CDT-1 degradation during S phase and for restraining DNA rereplication.

Core Functions

Adaptor/scaffold of CRL4 ligases: binds CUL-4 and DCAF substrate receptors (CDT-2, WDR-23) and substrates such as CDT-1, enabling their ubiquitination and proteasomal degradation.

Molecular Function:
ubiquitin ligase complex scaffold activity
Directly Involved In:
protein ubiquitination proteasome-mediated ubiquitin-dependent protein catabolic process
Cellular Locations:
nucleus
In Complex:
Cul4-RING E3 ubiquitin ligase complex
Supporting Evidence:
  • PMID:17145765
    DDB-1 interacts specifically with CUL-4, but not with other cullins, in the yeast two-hybrid assay
  • PMID:17145765
    DDB-1 physically associates with CDT-1, indicating that CDT-1 is a direct substrate of the CUL-4/DDB-1 complex.
  • PMID:19273594
    SKN-1 protein levels, nuclear accumulation, and activity are repressed by the WD40 repeat protein WDR-23, which interacts with the CUL-4/DDB-1 ubiquitin ligase to presumably target the transcription factor for proteasomal degradation.

References

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Suggested Questions for Experts

Q: Does worm DDB-1 participate in nucleotide excision repair, and if so which DCAF provides damaged-DNA recognition in the absence of a characterised worm DDB2 counterpart?

Suggested Experiments

Experiment: UV sensitivity and CPD-removal assays in ddb-1 hypomorphs or germline-specific depletion to test a conserved DNA-repair role.

Deep Research

WormBase

(ddb-1-deep-research-wormbase.md)
WormBase gene description for ddb-1 (worm) WormBase

WormBase gene description for ddb-1 (worm)

ddb-1 encodes a protein orthologous to human DNA damage-binding protein 1 (DDB1); ddb-1 is part of a ubiquitin ligase E3 complex, CUL-4/DDB-1, and targets the replication licensing factor, cdt-1, for ubiquitin-mediated proteolysis; ddb-1 interacts physically with CUL-4/Cullin and CDT-1; the CUL-4/DDB-1 complex also regulates SKN-1 transcription factor activity, and LET-23/EGFR signalling in vulval precursor cells.

📚 Additional Documentation

Notes

(ddb-1-notes.md)

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