DDB1
The protein encoded by this gene is the large subunit (p127) of the heterodimeric DNA damage-binding (DDB) complex while another protein (p48) forms the small subunit. This protein complex functions in nucleotide-excision repair and binds to DNA following UV damage. Defective activity of this complex causes the repair defect in patients with xeroderma pigmentosum complementation group E (XPE) - an autosomal recessive disorder characterized by photosensitivity and early onset of carcinomas. However, it remains for mutation analysis to demonstrate whether the defect in XPE patients is in this gene or the gene encoding the small subunit. In addition, Best vitelliform mascular dystrophy is mapped to the same region as this gene on 11q, but no sequence alternations of this gene are demonstrated in Best disease patients. The protein encoded by this gene also functions as an adaptor molecule for the cullin 4 (CUL4) ubiquitin E3 ligase complex by facilitating the binding of substrates to this complex and the ubiquitination of proteins. [provided by RefSeq, May 2012]
Function
Protein, which is both involved in DNA repair and protein ubiquitination, as part of the UV-DDB complex and DCX (DDB1-CUL4-X-box) complexes, respectively (PubMed:15448697, PubMed:14739464, PubMed:16260596, PubMed:16482215, PubMed:17079684, PubMed:16407242, PubMed:16407252, PubMed:16940174).
Core component of the UV-DDB complex (UV-damaged DNA-binding protein complex), a complex that recognizes UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair (PubMed:15448697, PubMed:16260596, PubMed:16407242, PubMed:16940174).
The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches (PubMed:15448697, PubMed:16260596, PubMed:16407242, PubMed:16940174).
Also functions as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:14739464, PubMed:16407252, PubMed:16482215, PubMed:17079684, PubMed:25043012, PubMed:25108355, PubMed:18332868, PubMed:18381890, PubMed:19966799, PubMed:22118460, PubMed:28886238).
The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1 (PubMed:14739464, PubMed:16407252, PubMed:16482215, PubMed:17079684, PubMed:25043012, PubMed:25108355, PubMed:18332868, PubMed:18381890, PubMed:19966799, PubMed:22118460).
DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage (PubMed:16678110, PubMed:17041588, PubMed:16473935, PubMed:18593899).
The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair (PubMed:16678110, PubMed:17041588, PubMed:16473935, PubMed:18593899).
DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER (PubMed:15882621).
DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication (PubMed:17041588).
DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR) (PubMed:12732143).
The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1 (PubMed:26431207).
DDB1-mediated CRY1 degradation promotes FOXO1 protein stability and FOXO1-mediated gluconeogenesis in the liver (By similarity).
Biological Process
Biological process involved in interaction with symbiont Source: AgBase
Cellular response to DNA damage stimulus Source: UniProtKB
DNA damage response, detection of DNA damage Source: Reactome
DNA repair Source: GO_Central
Global genome nucleotide-excision repair Source: Reactome
Histone H2A monoubiquitination Source: UniProtKB
Nucleotide-excision repair Source: ProtInc
Nucleotide-excision repair, DNA damage recognition Source: Reactome
Nucleotide-excision repair, DNA duplex unwinding Source: Reactome
Nucleotide-excision repair, DNA incision Source: Reactome
Nucleotide-excision repair, DNA incision, 3'-to lesion Source: Reactome
Nucleotide-excision repair, DNA incision, 5'-to lesion Source: Reactome
Nucleotide-excision repair, preincision complex assembly Source: Reactome
Nucleotide-excision repair, preincision complex stabilization Source: Reactome
Positive regulation by virus of viral protein levels in host cell Source: AgBase
Positive regulation of gluconeogenesis Source: UniProtKB
Positive regulation of protein catabolic process Source: UniProtKB
Positive regulation of viral genome replication Source: AgBase
Positive regulation of viral release from host cell Source: AgBase
Post-translational protein modification Source: Reactome
Proteasomal protein catabolic process Source: MGI
Proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
Protein ubiquitination Source: UniProtKB
Regulation of mitotic cell cycle phase transition Source: UniProtKB
Rhythmic process Source: UniProtKB-KW
Transcription-coupled nucleotide-excision repair Source: Reactome
Ubiquitin-dependent protein catabolic process Source: UniProtKB
UV-damage excision repair Source: UniProtKB
Viral process Source: UniProtKB-KW