Atlas of Genetics and Cytogenetics in Oncology and Haematology


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XPE (xeroderma pigmentosum, complementation group E)

Identity

Other namesUV-DDB
DDB2
Hugo DDB2
Location 11p12-11p11
 
  XPE (11p11) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are welcome : contact rocchi@biologia.uniba.it

DNA/RNA

Transcription 4193 bp

Protein

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 xeroderma pigmentosum, XP group E
Oncogenesis Early skin tumours
  

External links

Nomenclature
HugoDDB2
GDBDDB2
Entrez_GeneDDB2  1643  damage-specific DNA binding protein 2, 48kDa
Cards
AtlasXPEID298
GeneCardsDDB2
EnsemblDDB2 [Search_View]   ENSG00000134574 [Gene_View]
GenatlasDDB2
GeneLynxDDB2
eGenomeDDB2
euGene1643
Genomic and cartography
GoldenPathDDB2  -     chr11:47193089-47217339 +  11p12-p11   [Description]    (hg18-Mar_2006)
EnsemblDDB2 - 11p12-p11 [CytoView]
NCBIMapview
OMIMDisease map [OMIM]
HomoloGeneDDB2
Gene and transcription
GenbankAA278953 [ ENTREZ ]
GenbankAB107037 [ ENTREZ ]
GenbankAB107038 [ ENTREZ ]
GenbankAB107039 [ ENTREZ ]
GenbankAB107040 [ ENTREZ ]
RefSeqNM_000107 [ SRS ]    NM_000107 [ ENTREZ ]
RefSeqAC_000054 [ SRS ]    AC_000054 [ ENTREZ ]
RefSeqNC_000011 [ SRS ]    NC_000011 [ ENTREZ ]
RefSeqNT_009237 [ SRS ]    NT_009237 [ ENTREZ ]
RefSeqNW_925006 [ SRS ]    NW_925006 [ ENTREZ ]
AceViewDDB2 AceView - NCBI
UnigeneHs.702063 [ SRS ]    Hs.702063 [ NCBI ]     HS702063 [ spliceNest ]
Fast-db5834 (alternative variants)
Protein : pattern, domain, 3D structure
SwissProtQ92466 [ SRS]    Q92466 [ EXPASY ]     Q92466 [ INTERPRO ]
PrositePS00678 WD_REPEATS_1 [ SRS ]    PS00678 WD_REPEATS_1 [ Expasy ]
PrositePS50082 WD_REPEATS_2 [ SRS ]    PS50082 WD_REPEATS_2 [ Expasy ]
PrositePS50294 WD_REPEATS_REGION [ SRS ]    PS50294 WD_REPEATS_REGION [ Expasy ]
InterproIPR015943 WD40/YVTN_repeat-like [ SRS ]    IPR015943 WD40/YVTN_repeat-like [ EBI ]
InterproIPR001680 WD40_repeat [ SRS ]    IPR001680 WD40_repeat [ EBI ]
CluSTrQ92466
PfamPF00400 WD40 [ SRS ]    PF00400 WD40 [ Sanger ]    pfam00400 [ NCBI-CDD ]
SmartSM00320 WD40 [EMBL]
BlocksQ92466
HPRD02886
Protein Interaction databases
DIPQ92466
IntActQ92466
Polymorphism : SNP, mutations, diseases
OMIM278740;600811    [ map ]   
GENECLINICS278740;600811
SNPDDB2 [dbSNP-NCBI]  
SNPNM_000107 [SNP-NCI]  
SNPDDB2 [GeneSNPs - Utah]  DDB2] [HGBASE - SRS]
HAPMAPDDB2 [HAPMAP]  
COSMICDDB2 [Somatic mutation (COSMIC-CGP-Sanger)]  
HGMDDDB2
General knowledge
Family BrowserDDB2 [UCSC Family Browser]
SOURCENM_000107
SMDHs.702063
SAGEHs.702063
GOprotein polyubiquitination [Amigo]  protein polyubiquitination
GOdamaged DNA binding [Amigo]  damaged DNA binding
GOubiquitin-protein ligase activity [Amigo]  ubiquitin-protein ligase activity
GOprotein binding [Amigo]  protein binding
GOnucleus [Amigo]  nucleus
GOnucleotide-excision repair [Amigo]  nucleotide-excision repair
GOresponse to UV [Amigo]  response to UV
GOprotein complex [Amigo]  protein complex
GOprotein autoubiquitination [Amigo]  protein autoubiquitination
PubGeneDDB2
TreeFamDDB2
CTD1643 [Comparative ToxicoGenomics Database]
Other databases
Probes
ProbeCancer Cytogenetics (Bari)
ProbeDDB2 Related clones (RZPD - Berlin)
PubMed
PubMed39 Pubmed reference(s) in LocusLink

Bibliography

Induction of a novel damage-specific DNA binding protein correlates with enhanced DNA repair in primate cells.
Proti M, Hirschfeld S, Tsang AP, Wagner M, Dixon K, Levine AS
Molecular toxicology. 1989 ; 2 (4) : 255-270.
PMID 2518795
 
Purification of an ultraviolet-inducible, damage-specific DNA-binding protein from primate cells.
Abrami M, Levine AS, Proti M
The Journal of biological chemistry. 1991 ; 266 (33) : 22493-22500.
PMID 1657999
 
Comparative 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, Nichols AF, Keeney S, Smith CA, Taylor JS, Linn S, Sancar A
The Journal of biological chemistry. 1993 ; 268 (28) : 21301-21308.
PMID 8407968
 
A 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, Abramic M, Moos M Jr, Otrin VR, Wootton JC, McLenigan M, Levine AS, Protic M
Nucleic acids research. 1993 ; 21 (17) : 4111-4118.
PMID 8371985
 
Mammalian DNA nucleotide excision repair reconstituted with purified protein components.
Aboussekhra A, Biggerstaff M, Shivji MK, Vilpo JA, Moncollin V, Podust VN, Proti M, Hbscher U, Egly JM, Wood RD
Cell. 1995 ; 80 (6) : 859-868.
PMID 7697716
 
Chromosomal 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, Brody T, Keeney S, Nichols AF, Admon A, Linn S
Genomics. 1995 ; 29 (1) : 62-69.
PMID 8530102
 
Isolation of a cDNA encoding a UV-damaged DNA binding factor defective in xeroderma pigmentosum group E cells.
Hwang BJ, Liao JC, Chu G
Mutation research. 1996 ; 362 (1) : 105-117.
PMID 8538642
 
Functional complementation of xeroderma pigmentosum complementation group E by replication protein A in an in vitro system.
Kazantsev A, Mu D, Nichols AF, Zhao X, Linn S, Sancar A
Proceedings of the National Academy of Sciences of the United States of America. 1996 ; 93 (10) : 5014-5018.
PMID 8643521
 
Mutations specific to the xeroderma pigmentosum group E Ddb- phenotype.
Nichols AF, Ong P, Linn S
The Journal of biological chemistry. 1996 ; 271 (40) : 24317-24320.
PMID 8798680
 
Translocation of a UV-damaged DNA binding protein into a tight association with chromatin after treatment of mammalian cells with UV light.
Otrin VR, McLenigan M, Takao M, Levine AS, Proti M
Journal of cell science. 1997 ; 110 ( Pt 10) : 1159-1168.
PMID 9191040
 
DDB, a putative DNA repair protein, can function as a transcriptional partner of E2F1.
Hayes S, Shiyanov P, Chen X, Raychaudhuri P
Molecular and cellular biology. 1998 ; 18 (1) : 240-249.
PMID 9418871
 
The V protein of the paramyxovirus SV5 interacts with damage-specific DNA binding protein.
Lin GY, Paterson RG, Richardson CD, Lamb RA
Virology. 1998 ; 249 (1) : 189-200.
PMID 9740790
 
Relationship of the xeroderma pigmentosum group E DNA repair defect to the chromatin and DNA binding proteins UV-DDB and replication protein A.
Rapi Otrin V, Kuraoka I, Nardo T, McLenigan M, Eker AP, Stefanini M, Levine AS, Wood RD
Molecular and cellular biology. 1998 ; 18 (6) : 3182-3190.
PMID 9584159
 
Refined 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.
Sthr H, Marquardt A, Rivera A, Kellner U, Weber BH
European journal of human genetics : EJHG. 1998 ; 6 (4) : 400-405.
PMID 9781049
 
A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy.
Cleaver JE, Thompson LH, Richardson AS, States JC
Human mutation. 1999 ; 14 (1) : 9-22.
PMID 10447254
 
Characterization of DNA recognition by the human UV-damaged DNA-binding protein.
Fujiwara Y, Masutani C, Mizukoshi T, Kondo J, Hanaoka F, Iwai S
The Journal of biological chemistry. 1999 ; 274 (28) : 20027-20033.
PMID 10391953
 
Expression of the p48 xeroderma pigmentosum gene is p53-dependent and is involved in global genomic repair.
Hwang BJ, Ford JM, Hanawalt PC, Chu G
Proceedings of the National Academy of Sciences of the United States of America. 1999 ; 96 (2) : 424-428.
PMID 9892649
 
A 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, Mori T, Ohkubo H, Yamaizumi M
The Journal of investigative dermatology. 1999 ; 113 (2) : 251-257.
PMID 10469312
 
DNA structures recognized by the human UV-DDB protein.
Mizukoshi T, Fujiwara Y, Iwai S
Nucleic acids symposium series. 1999 : 265-266.
PMID 10780481
 
The naturally occurring mutants of DDB are impaired in stimulating nuclear import of the p125 subunit and E2F1-activated transcription.
Shiyanov P, Hayes SA, Donepudi M, Nichols AF, Linn S, Slagle BL, Raychaudhuri P
Molecular and cellular biology. 1999 ; 19 (7) : 4935-4943.
PMID 10373543
 
Cullin 4A associates with the UV-damaged DNA-binding protein DDB.
Shiyanov P, Nag A, Raychaudhuri P
The Journal of biological chemistry. 1999 ; 274 (50) : 35309-35312.
PMID 10585395
 
Effect of DNA lesions on transcription elongation.
Tornaletti S, Hanawalt PC
Biochimie. 1999 ; 81 (1-2) : 139-146.
PMID 10214918
 
A 127-kDa protein (UV-DDB) binds to the cytoplasmic domain of the Alzheimer's amyloid precursor protein.
Watanabe T, Sukegawa J, Sukegawa I, Tomita S, Iijima K, Oguchi S, Suzuki T, Nairn AC, Greengard P
Journal of neurochemistry. 1999 ; 72 (2) : 549-556.
PMID 9930726
 
Reinvestigation of the classification of five cell strains of xeroderma pigmentosum group E with reclassification of three of them.
Itoh T, Linn S, Ono T, Yamaizumi M
The Journal of investigative dermatology. 2000 ; 114 (5) : 1022-1029.
PMID 10771487
 
Nuclear transport of human DDB protein induced by ultraviolet light.
Liu W, Nichols AF, Graham JA, Dualan R, Abbas A, Linn S
The Journal of biological chemistry. 2000 ; 275 (28) : 21429-21434.
PMID 10777491
 
Human damage-specific DNA-binding protein p48. Characterization of XPE mutations and regulation following UV irradiation.
Nichols AF, Itoh T, Graham JA, Liu W, Yamaizumi M, Linn S
The Journal of biological chemistry. 2000 ; 275 (28) : 21422-21428.
PMID 10777490
 
Correct binding of viral X protein to UVDDB-p127 cellular protein is critical for efficient infection by hepatitis B viruses.
Sitterlin D, Bergametti F, Tiollais P, Tennant BC, Transy C
Oncogene. 2000 ; 19 (38) : 4427-4431.
PMID 10980618
 
UVDDB p127-binding modulates activities and intracellular distribution of hepatitis B virus X protein.
Sitterlin D, Bergametti F, Transy C
Oncogene. 2000 ; 19 (38) : 4417-4426.
PMID 10980617
 
Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UV-induced mutagenesis.
Tang JY, Hwang BJ, Ford JM, Hanawalt PC, Chu G
Molecular cell. 2000 ; 5 (4) : 737-744.
PMID 10882109
 
Cloning and characterization of a senescence inducing and class II tumor suppressor gene in ovarian carcinoma at chromosome region 6q27.
Acquati F, Morelli C, Cinquetti R, Bianchi MG, Porrini D, Varesco L, Gismondi V, Rocchetti R, Talevi S, Possati L, Magnanini C, Tibiletti MG, Bernasconi B, Daidone MG, Shridhar V, Smith DI, Negrini M, Barbanti-Brodano G, Taramelli R
Oncogene. 2001 ; 20 (8) : 980-988.
PMID 11314033
 
The p48 subunit of the damaged-DNA binding protein DDB associates with the CBP/p300 family of histone acetyltransferase.
Datta A, Bagchi S, Nag A, Shiyanov P, Adami GR, Yoon T, Raychaudhuri P
Mutation research. 2001 ; 486 (2) : 89-97.
PMID 11425514
 
Genetically determined susceptibility markers in skin cancer and their application to chemoprevention.
Hahn H
IARC scientific publications. 2001 ; 154 : 93-100.
PMID 11220672
 
Controlling the efficiency of excision repair.
Hanawalt PC
Mutation research. 2001 ; 485 (1) : 3-13.
PMID 11341989
 
Importance of DNA repair in carcinogenesis: evidence from transgenic and gene targeting studies.
Ishikawa T, Ide F, Qin X, Zhang S, Takahashi Y, Sekiguchi M, Tanaka K, Nakatsuru Y
Mutation research. 2001 ; 477 (1-2) : 41-49.
PMID 11376685
 
Damaged DNA-binding protein DDB stimulates the excision of cyclobutane pyrimidine dimers in vitro in concert with XPA and replication protein A.
Wakasugi M, Shimizu M, Morioka H, Linn S, Nikaido O, Matsunaga T
The Journal of biological chemistry. 2001 ; 276 (18) : 15434-15440.
PMID 11278856
 
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Contributor(s)

Written09-2001Anne Stary, Alain Sarasin

Citation

This paper should be referenced as such :
Stary A, Sarasin A . XPE (xeroderma pigmentosum, complementation group E). Atlas Genet Cytogenet Oncol Haematol. September 2001 .
URL : http://AtlasGeneticsOncology.org/Genes/XPEID298.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Jul 2 08:28:07 2008


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