DDB2 (xeroderma pigmentosum, complementation group E)

2001-09-01   Anne Stary , Alain Sarasin 

Laboratory of Genetic Instability, Cancer, UPR2169 CNRS, Institut de Recherches sur le Cancer, 7, rue guy Moquet, BP 8, 94801 VILLEJUIF, France

Identity

HGNC
LOCATION
11p11.2
IMAGE
Atlas Image
LEGEND
XPE (11p11) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
LOCUSID
ALIAS
DDBB,UV-DDB2,XPE
FUSION GENES

DNA/RNA

Transcription

4193 bp

Proteins

Description

DDB1: 1140 amino acids, 127 kDa; DDB2: 427 amino acids, 48 kDa; DDB1 (p127) and DDB2 (p48) form a stable heterodimer UV-DDB

Function

The damage-specific DNA binding (UV-DDB) activity purified as a heterodimer (p127 and p48) is expected to play a role in damage recognition prior to the Nucleotide Excision Repair (NER) because the DDB protein is reported to recognize many types of DNA lesions and is inducible by treatment with DNA-damaging agents. After UV irradiation, dynamic nuclear accumulation of DDB1 from the cytoplasm was found after 24 h. The function of the gene product is not completely clarified yet. Band shift assays suggested that the XPE gene product acts as a damaged DNA binding protein (DDB), with high affinity to UV-induced 6-4Pyrimidine-Pyrimidone photoproducts. However, defective DDB binding activity is not a common feature of XPE mutant cell lines and in fact two (or even more) proteins may be involved in the binding activity: p48 and p125. In cells from several XPE patient mutations in p48 have been found but so far no mutations have been found in the p125 gene. XPE patients show mild dermatological symptoms and cells from these patients have a relatively high repair capacity. XPE cells are not necessarily defective in repair: p125 is proposed to play a role in opening up chromatin to make CPD accessible to the NER machinery, but is not required for repair of 6-4PP. Interestingly, cell lines and primary tissues from rodents are fully deficient in the expression of the p48 protein . This explains the absence of GGR of CPD in these cells. Exogenous expression of p48 in hamster cells confers enhanced removal of CPD from genomic DNA and nontranscribed strand of active genes. The p48 protein is upregulated by p53.

Mutations

Germinal

three single base substitutions only in DDB2 (p48) gene

Implicated in

Entity name
xeroderma pigmentosum, XP group E
Oncogenesis
Early skin tumours

Bibliography

Pubmed IDLast YearTitleAuthors
76977161995Mammalian DNA nucleotide excision repair reconstituted with purified protein components.Aboussekhra A et al
16579991991Purification of an ultraviolet-inducible, damage-specific DNA-binding protein from primate cells.Abramić M et al
113140332001Cloning and characterization of a senescence inducing and class II tumor suppressor gene in ovarian carcinoma at chromosome region 6q27.Acquati F et al
104472541999A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy.Cleaver JE et al
114255142001The p48 subunit of the damaged-DNA binding protein DDB associates with the CBP/p300 family of histone acetyltransferase.Datta A et al
85301021995Chromosomal localization and cDNA cloning of the genes (DDB1 and DDB2) for the p127 and p48 subunits of a human damage-specific DNA binding protein.Dualan R et al
103919531999Characterization of DNA recognition by the human UV-damaged DNA-binding protein.Fujiwara Y et al
112206722001Genetically determined susceptibility markers in skin cancer and their application to chemoprevention.Hahn H et al
113419892001Controlling the efficiency of excision repair.Hanawalt PC et al
94188711998DDB, a putative DNA repair protein, can function as a transcriptional partner of E2F1.Hayes S et al
98926491999Expression of the p48 xeroderma pigmentosum gene is p53-dependent and is involved in global genomic repair.Hwang BJ et al
85386421996Isolation of a cDNA encoding a UV-damaged DNA binding factor defective in xeroderma pigmentosum group E cells.Hwang BJ et al
113766852001Importance of DNA repair in carcinogenesis: evidence from transgenic and gene targeting studies.Ishikawa T et al
107714872000Reinvestigation of the classification of five cell strains of xeroderma pigmentosum group E with reclassification of three of them.Itoh T et al
104693121999A newly identified patient with clinical xeroderma pigmentosum phenotype has a non-sense mutation in the DDB2 gene and incomplete repair in (6-4) photoproducts.Itoh T et al
86435211996Functional complementation of xeroderma pigmentosum complementation group E by replication protein A in an in vitro system.Kazantsev A et al
97407901998The V protein of the paramyxovirus SV5 interacts with damage-specific DNA binding protein.Lin GY et al
107774912000Nuclear transport of human DDB protein induced by ultraviolet light.Liu W et al
107804811999DNA structures recognized by the human UV-DDB protein.Mizukoshi T et al
107774902000Human damage-specific DNA-binding protein p48. Characterization of XPE mutations and regulation following UV irradiation.Nichols AF et al
91910401997Translocation of a UV-damaged DNA binding protein into a tight association with chromatin after treatment of mammalian cells with UV light.Otrin VR et al
25187951989Induction of a novel damage-specific DNA binding protein correlates with enhanced DNA repair in primate cells.Protić M et al
95841591998Relationship of the xeroderma pigmentosum group E DNA repair defect to the chromatin and DNA binding proteins UV-DDB and replication protein A.Rapić Otrin V et al
84079681993Comparative analysis of binding of human damaged DNA-binding protein (XPE) and Escherichia coli damage recognition protein (UvrA) to the major ultraviolet photoproducts: T[c,s]T, T[t,s]T, T[6-4]T, and T[Dewar]T.Reardon JT et al
105853951999Cullin 4A associates with the UV-damaged DNA-binding protein DDB.Shiyanov P et al
109806172000UVDDB p127-binding modulates activities and intracellular distribution of hepatitis B virus X protein.Sitterlin D et al
97810491998Refined mapping of the gene encoding the p127 kDa UV-damaged DNA-binding protein (DDB1) within 11q12-q13.1 and its exclusion in Best's vitelliform macular dystrophy.Stöhr H et al
83719851993A 127 kDa component of a UV-damaged DNA-binding complex, which is defective in some xeroderma pigmentosum group E patients, is homologous to a slime mold protein.Takao M et al
108821092000Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UV-induced mutagenesis.Tang JY et al
102149181999Effect of DNA lesions on transcription elongation.Tornaletti S et al
112788562001Damaged DNA-binding protein DDB stimulates the excision of cyclobutane pyrimidine dimers in vitro in concert with XPA and replication protein A.Wakasugi M et al
99307261999A 127-kDa protein (UV-DDB) binds to the cytoplasmic domain of the Alzheimer's amyloid precursor protein.Watanabe T et al

Other Information

Locus ID:

NCBI: 1643
MIM: 600811
HGNC: 2718
Ensembl: ENSG00000134574

Variants:

dbSNP: 1643
ClinVar: 1643
TCGA: ENSG00000134574
COSMIC: DDB2

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000134574ENST00000256996Q92466
ENSG00000134574ENST00000378600Q92466
ENSG00000134574ENST00000378601Q92466
ENSG00000134574ENST00000378603Q92466
ENSG00000134574ENST00000610805A0A087WTQ7
ENSG00000134574ENST00000614825A0A087X0X5
ENSG00000134574ENST00000616278Q92466
ENSG00000134574ENST00000617847A0A087WYT8
ENSG00000134574ENST00000622090A0A087WW71
ENSG00000134574ENST00000622878A0A087WV56

Expression (GTEx)

0
10
20
30
40
50
60
70
80
90
100

Pathways

PathwaySourceExternal ID
Nucleotide excision repairKEGGko03420
p53 signaling pathwayKEGGko04115
Ubiquitin mediated proteolysisKEGGko04120
Nucleotide excision repairKEGGhsa03420
p53 signaling pathwayKEGGhsa04115
Ubiquitin mediated proteolysisKEGGhsa04120
Cul4-DDB1-DDB2 complexKEGGhsa_M00385
Hepatitis BKEGGhsa05161
Cul4-DDB1-DDB2 complexKEGGM00385
Metabolism of proteinsREACTOMER-HSA-392499
Post-translational protein modificationREACTOMER-HSA-597592
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Transcriptional Regulation by TP53REACTOMER-HSA-3700989
DNA RepairREACTOMER-HSA-73894
Nucleotide Excision RepairREACTOMER-HSA-5696398
Global Genome Nucleotide Excision Repair (GG-NER)REACTOMER-HSA-5696399
DNA Damage Recognition in GG-NERREACTOMER-HSA-5696394
Formation of Incision Complex in GG-NERREACTOMER-HSA-5696395
Dual Incision in GG-NERREACTOMER-HSA-5696400
TP53 Regulates Transcription of DNA Repair GenesREACTOMER-HSA-6796648
DeubiquitinationREACTOMER-HSA-5688426
Ub-specific processing proteasesREACTOMER-HSA-5689880

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
127321432003The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage.265
158826212005UV-induced ubiquitylation of XPC protein mediated by UV-DDB-ubiquitin ligase complex.235
191098932008Structural basis of UV DNA-damage recognition by the DDB1-DDB2 complex.156
164739352006The DDB1-CUL4ADDB2 ubiquitin ligase is deficient in xeroderma pigmentosum group E and targets histone H2A at UV-damaged DNA sites.142
129443862003In vivo recruitment of XPC to UV-induced cyclobutane pyrimidine dimers by the DDB2 gene product.81
230455482012PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1.76
165278072006Cullin 4A-mediated proteolysis of DDB2 protein at DNA damage sites regulates in vivo lesion recognition by XPC.71
224927242012DDB2 promotes chromatin decondensation at UV-induced DNA damage.60
119719582002p53 Binds and activates the xeroderma pigmentosum DDB2 gene in humans but not mice.59
185938992008The cullin 4B-based UV-damaged DNA-binding protein ligase binds to UV-damaged chromatin and ubiquitinates histone H2A.53

Citation

Anne Stary ; Alain Sarasin

DDB2 (xeroderma pigmentosum, complementation group E)

Atlas Genet Cytogenet Oncol Haematol. 2001-09-01

Online version: http://atlasgeneticsoncology.org/gene/298/ddb2