DNA damage-binding protein 2; damage-specific DNA-binding protein 2; DDB p48 subunit; DDBb; UV-damaged DNA-binding protein 2; UV-DDB 2 (DDB2)
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Function
- required for DNA repair
- binds to DDB1 to form the UV-DDB complex (UV-damaged DNA-binding protein complex)
- isoform D1 & isoform D2 inhibit UV-damaged DNA repair
- protein modification; protein ubiquitination
- ubiquitinated by CUL4A in response to UV irradiation
- ubiquitination appears to both impair DNA-binding & promotes ubiquitin-dependent proteolysis
- degradation of DDB2 at sites of DNA damage may be a prerequisite for their recognition by XPC & subsequent repair
- CUL4A-mediated degradation appears to be promoted by ABL1/c-ABL
- the UV-DDB complex interacts with monoubiquitinated histone H2A & binds to XPC via the DDB2 subunit
- component of the DCX complex
- DDB2 may function as the substrate recognition module within this complex.
- a large number of other DCX complexes may also exist in which an alternate substrate targeting subunit replaces DDB2 as a substrate recognition modue
- these targeting subunits are generally known as
- DCAF (DDB1-&-CUL4-associated factor) or
- CDW (CUL4-DDB1-associated WD40-repeat)
- these targeting subunits are generally known as
- isoform D1 & isoform D2 do not interact with DDB1
Structure
- the DWD box is required for interaction with DDB1
- belongs to the WD repeat DDB2/WDR76 family
- contains 5 WD repeats
Compartment
- nucleus
- accumulates at sites of DNA damage following UV irradiation
Alternative splicing
named isoforms=5; D1, D2, D3, D4
Expression
- ubiquitously expressed
- highest levels in corneal endothelium
- lowest levels in brain
- isoform D1 is highly expressed in brain & heart
- isoform D2, isoform D3 & isoform D4 are weakly expressed
- induced in response to treatment with IR or UV & this requires p53 activity
Pathology
- defects in DDB2 are a cause of xeroderma pigmentosum complementation group E (XP-E)
More general terms
Component of
References
- ↑ UniProt http://www.uniprot.org/uniprot/Q92466.html
- ↑ Allelic variations of the XP genes http://www.xpmutations.org/
- ↑ Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/XPEID298.html
- ↑ GeneReviews http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/DDB2
- ↑ NIEHS-SNPs http://egp.gs.washington.edu/data/ddb2/