ERCC2 (Excision repair cross-complementing rodent repair deficiency, complementation group 2)

2001-02-01   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
ERCC2
LOCATION
19q13.32
IMAGE
Atlas Image
LEGEND
XPD (19q13) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
LOCUSID
2068
ALIAS
COFS2,EM9,TFIIH,TTD,TTD1,XPD
FUSION GENES
Show Gene Fusions

DNA/RNA

Description

54336 bp; 23 exons

Transcription

2400b mRNA

Proteins

Description

760 amino acids

Expression

ubiquitous

Localisation

nuclear

Function

5-3 ATP-dependent helicase activity involved in DNA excision repair (NER) and as a subunit of the basal transcription factor TFIIH
The XPD gene product displayed 5-3 helicase activity. The XPD as the XPB protein are also found in the transcription factor TFIIH, a large complex involved in the initiation of transcription The striking discovery that subunits of basal transcription factor TFIIH were involved in Nucleotide Excision Repair (NER) sheds light on a new aspect of NER : a close coupling to transcription via common use of essential factors. TFIIH fulfills a dual role in transcription initiation and NER and the role of TFIIH in NER might closely mimic its role in the transcription initiation process. In transcription initiation TFIIH is thought to be involved in unwinding of the promoter site and to allow promoter clearance. In the NER process TFIIH causes unwinding of the damage containing region that has been localized by XPC-HR23B and XPA-RPA, enabling the accumulation of NER proteins around the damaged site. Contrarely to the XPB helicase, the helicase activity of XPD is indispensable for NER but not for transcription initiation. So, there is much more XPD patients, and only two patients have been described as XP and CS.

Homology

FLYBASE :Xpd ; MGI : Ercc2 (Nb 95413)

Mutations

Germinal

17 mutated sites associated with the xeroderma pigmentosum group D syndrome (among them 3 are also associated with the Cockaynesyndrome) and 15 mutated sites associated with the trichothiodystrophy syndrome

Implicated in

Entity name
xeroderma pigmentosum (XP), XP associated with Cockayne syndrome (CS), and trichothiodystrophy (TTD)
Disease
predisposition to skin cancer: early skin cancers (XPD). Mental and stature abnormalities (XP/CS, and TTD)

Article Bibliography

Pubmed IDLast YearTitleAuthors
76977161995Mammalian DNA nucleotide excision repair reconstituted with purified protein components.Aboussekhra A et al
91926521997Photocarcinogenesis and inhibition of intercellular adhesion molecule 1 expression in cells of DNA-repair-defective individuals.Ahrens C et al
106735062000Nucleotide excision repair of DNA with recombinant human proteins: definition of the minimal set of factors, active forms of TFIIH, and modulation by CAK.Araújo SJ et al
106675982000The cancer-free phenotype in trichothiodystrophy is unrelated to its repair defect.Berneburg M et al
97586211998Analysis of mutations in the XPD gene in Italian patients with trichothiodystrophy: site of mutation correlates with repair deficiency, but gene dosage appears to determine clinical severity.Botta E et al
106447102000Distinct roles for the helicases of TFIIH in transcript initiation and promoter escape.Bradsher J et al
79206401994Mutations in the xeroderma pigmentosum group D DNA repair/transcription gene in patients with trichothiodystrophy.Broughton BC et al
85907351995Functional retroviral vector for gene therapy of xeroderma pigmentosum group D patients.Carreau M et al
109490342000Activation of estrogen receptor alpha by S118 phosphorylation involves a ligand-dependent interaction with TFIIH and participation of CDK7.Chen D et al
90259071997Quantitation of ERCC-2 gene expression in human tumor cell lines by reverse transcription-polymerase chain reaction in comparison to northern blot analysis.Chen ZP et al
96571421998Hair today, gone tomorrow: transgenic mice with human repair deficient hair disease.Cleaver JE et al
100646011999Mutations in XPB and XPD helicases found in xeroderma pigmentosum patients impair the transcription function of TFIIH.Coin F et al
97717131998Mutations in the XPD helicase gene result in XP and TTD phenotypes, preventing interaction between XPD and the p44 subunit of TFIIH.Coin F et al
92784841997Reduced RNA polymerase II transcription in extracts of cockayne syndrome and xeroderma pigmentosum/Cockayne syndrome cells.Dianov GL et al
86928421996Human cyclin-dependent kinase-activating kinase exists in three distinct complexes.Drapkin R et al
81524901994Dual role of TFIIH in DNA excision repair and in transcription by RNA polymerase II.Drapkin R et al
97719451998Recovery of the normal p53 response after UV treatment in DNA repair-deficient fibroblasts by retroviral-mediated correction with the XPD gene.Dumaz N et al
94334781997Prolonged p53 protein accumulation in trichothiodystrophy fibroblasts dependent on unrepaired pyrimidine dimers on the transcribed strands of cellular genes.Dumaz N et al
93518361997Mechanism of open complex and dual incision formation by human nucleotide excision repair factors.Evans E et al
88247721995Stable SV40-transformation and characterisation of some DNA repair properties of fibroblasts from a trichothiodystrophy patient.Eveno E et al
17296951992Correction of xeroderma pigmentosum complementation group D mutant cell phenotypes by chromosome and gene transfer: involvement of the human ERCC2 DNA repair gene.Flejter WL et al
106040091999[Trichothiodystrophy: progresssive manifestations].Foulc P et al
78497021994Structural and mutational analysis of the xeroderma pigmentosum group D (XPD) gene.Frederick GD et al
80331041994The human DNA repair gene, ERCC2 (XPD), corrects ultraviolet hypersensitivity and ultraviolet hypermutability of a shuttle vector replicated in xeroderma pigmentosum group D cells.Gözükara EM et al
81077801994DNA repair gene RAD3 of S. cerevisiae is essential for transcription by RNA polymerase II.Guzder SN et al
76290611995Lethality in yeast of trichothiodystrophy (TTD) mutations in the human xeroderma pigmentosum group D gene. Implications for transcriptional defect in TTD.Guzder SN et al
97144611998Expression of DNA excision-repair-cross-complementing proteins p80 and p89 in brain of patients with Down Syndrome and Alzheimer's disease.Hermon M et al
91012921997Mutations in the XPD gene leading to xeroderma pigmentosum symptoms.Kobayashi T et al
86125851996Functional interactions between p53 and the TFIIH complex are affected by tumour-associated mutations.Léveillard T et al
87861411996Sequence analysis of the ERCC2 gene regions in human, mouse, and hamster reveals three linked genes.Lamerdin JE et al
107868322000Transcription-coupled repair of 8-oxoguanine: requirement for XPG, TFIIH, and CSB and implications for Cockayne syndrome.Le Page F et al
111566002001The xeroderma pigmentosum group D (XPD) gene: one gene, two functions, three diseases.Lehmann AR et al
83924421993UV-induced mutations in a shuttle vector replicated in repair deficient trichothiodystrophy cells differ with those in genetically-related cancer prone xeroderma pigmentosum.Madzak C et al
15350351992Immune defects in families and patients with xeroderma pigmentosum and trichothiodystrophy.Mariani E et al
75630731995Characteristics of UV-induced mutation spectra in human XP-D/ERCC2 gene-mutated xeroderma pigmentosum and trichothiodystrophy cells.Marionnet C et al
80556251994Correction by the ERCC2 gene of UV sensitivity and repair deficiency phenotype in a subset of trichothiodystrophy cells.Mezzina M et al
75103651994Molecular analysis of the XP-D gene in Italian families with patients affected by trichothiodystrophy and xeroderma pigmentosum group D.Mondello C et al
104287721999A role for the TFIIH XPB DNA helicase in promoter escape by RNA polymerase II.Moreland RJ et al
100965501999Differential behaviors toward ultraviolet A and B radiation of fibroblasts and keratinocytes from normal and DNA-repair-deficient patients.Otto AI et al
88552201996Hepatitis B virus transactivator protein, HBx, associates with the components of TFIIH and stimulates the DNA helicase activity of TFIIH.Qadri I et al
89601281996Long-term complementation of DNA repair deficient human primary fibroblasts by retroviral transduction of the XPD gene.Quilliet X et al
86928411996Isolation and characterization of two human transcription factor IIH (TFIIH)-related complexes: ERCC2/CAK and TFIIH.Reardon JT et al
106040011999[Trichothiodystrophies: anomalies of the repair and transcription of genes].Robert C et al
94275331997Competent transcription initiation by RNA polymerase II in cell-free extracts from xeroderma pigmentosum groups B and D in an optimized RNA transcription assay.Satoh MS et al
81945281994The ERCC2/DNA repair protein is associated with the class II BTF2/TFIIH transcription factor.Schaeffer L et al
110074782000Molecular structure of human TFIIH.Schultz P et al
76130921995TFIIH: a link between transcription, DNA repair and cell cycle regulation.Seroz T et al
109245142000p44/SSL1, the regulatory subunit of the XPD/RAD3 helicase, plays a crucial role in the transcriptional activity of TFIIH.Seroz T et al
13720951992DNA repair investigations in nine Italian patients affected by trichothiodystrophy.Stefanini M et al
111338112000XPD/ERCC2 polymorphisms and risk of head and neck cancer: a case-control analysis.Sturgis EM et al
84136721993Human xeroderma pigmentosum group D gene encodes a DNA helicase.Sung P et al
75856501995Defects in the DNA repair and transcription gene ERCC2 in the cancer-prone disorder xeroderma pigmentosum group D.Takayama K et al
92380331997Xeroderma pigmentosum and trichothiodystrophy are associated with different mutations in the XPD (ERCC2) repair/transcription gene.Taylor EM et al
100248821999Reconstitution of the transcription factor TFIIH: assignment of functions for the three enzymatic subunits, XPB, XPD, and cdk7.Tirode F et al
92523971997Sequence-specific and domain-specific DNA repair in xeroderma pigmentosum and Cockayne syndrome cells.Tu Y et al
110624692000Sublimiting concentration of TFIIH transcription/DNA repair factor causes TTD-A trichothiodystrophy disorder.Vermeulen W et al
110562912000DNA repair capacity: inconsistency between effect of over-expression of five NER genes and the correlation to mRNA levels in primary lymphocytes.Vogel U et al
85213831995Abrogation of p53-induced apoptosis by the hepatitis B virus X gene.Wang XW et al
86750091996The XPB and XPD DNA helicases are components of the p53-mediated apoptosis pathway.Wang XW et al
76635141995p53 modulation of TFIIH-associated nucleotide excision repair activity.Wang XW et al
81078881994Transcription factor b (TFIIH) is required during nucleotide-excision repair in yeast.Wang Z et al
80522701994Molecular analysis of CXPD mutations in the repair-deficient hamster mutants UV5 and UVL-13.Weber CA et al
21840311990ERCC2: cDNA cloning and molecular characterization of a human nucleotide excision repair gene with high homology to yeast RAD3.Weber CA et al
90124051997A mutation in the XPB/ERCC3 DNA repair transcription gene, associated with trichothiodystrophy.Weeda G et al
97716951998From a DNA helicase to brittle hair.Winkler GS et al
94153141997Retrovirus-mediated gene transfer corrects DNA repair defect of xeroderma pigmentosum cells of complementation groups A, B and C.Zeng L et al
94260631998Disruption of the mouse xeroderma pigmentosum group D DNA repair/basal transcription gene results in preimplantation lethality.de Boer J et al
96515811998A mouse model for the basal transcription/DNA repair syndrome trichothiodystrophy.de Boer J et al
104166151999Mouse model for the DNA repair/basal transcription disorder trichothiodystrophy reveals cancer predisposition.de Boer J et al
103905311999Cells from XP-D and XP-D-CS patients exhibit equally inefficient repair of UV-induced damage in transcribed genes but different capacity to recover UV-inhibited transcription.van Hoffen A et al

Other Information

Locus ID:

NCBI: 2068
MIM: 126340
HGNC: 3434
Ensembl: ENSG00000104884

Variants:

dbSNP: 2068
ClinVar: 2068
TCGA: ENSG00000104884
COSMIC: ERCC2

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000104884ENST00000391941A8MX75
ENSG00000104884ENST00000391944E7EVE9
ENSG00000104884ENST00000391945P18074
ENSG00000104884ENST00000485403P18074
ENSG00000104884ENST00000586131K7EIT8
ENSG00000104884ENST00000586856K7ENL1
ENSG00000104884ENST00000587376K7EKF3
ENSG00000104884ENST00000591309B4E0F6

Expression (GTEx)

0
5
10
15
20
25
30
35
40
45
Adipose - Subcutaneous
Adipose - Visceral
Adrenal Gland
Artery - Aorta
Artery - Tibial
Bladder
Brain - Amygdala
Brain - Anterior cingulate cortex
Brain - Caudate
Brain - Cerebellar Hemisphere
Brain - Cerebellum
Brain - Cortex
Brain - Frontal Cortex
Brain - Hippocampus
Brain - Hypothalamus
Brain - Nucleus accumbens
Brain - Putamen
Brain - Spinal cord
Brain - Substantia nigra
Breast - Mammary Tissue
Cells - Cultured fibroblasts
Cells - EBV - transformed lymphocytes
Cervix - Ectocervix
Cervix - Endocervix
Colon - Sigmoid
Colon - Transverse
Esophagus - Gastroesophageal Junction
Esophagus - Mucosa
Esophagus - Muscularis
Fallopian Tube
Heart - Atrial Appendage
Heart - Left Ventricle
Kidney - Cortex
Kidney - Medulla
Liver
Lung
Minor Salivary Gland
Muscle - Skeletal
Nerve - Tibial
Ovary
Pancreas
Pituitary
Prostate
Skin - Not Sun Exposed
Skin - Sun Exposed
Small Intestine - Terminal Ileum
Spleen
Stomach
Testis
Thyroid
Uterus
Vagina
Whole Blood

Pathways

PathwaySourceExternal ID
Basal transcription factorsKEGGko03022
Nucleotide excision repairKEGGko03420
Basal transcription factorsKEGGhsa03022
Nucleotide excision repairKEGGhsa03420
Holo-TFIIH complexKEGGhsa_M00290
Holo-TFIIH complexKEGGM00290
DiseaseREACTOMER-HSA-1643685
Infectious diseaseREACTOMER-HSA-5663205
HIV InfectionREACTOMER-HSA-162906
HIV Life CycleREACTOMER-HSA-162587
Late Phase of HIV Life CycleREACTOMER-HSA-162599
Transcription of the HIV genomeREACTOMER-HSA-167172
HIV Transcription InitiationREACTOMER-HSA-167161
RNA Polymerase II HIV Promoter EscapeREACTOMER-HSA-167162
RNA Pol II CTD phosphorylation and interaction with CE during HIV infectionREACTOMER-HSA-167160
HIV Transcription ElongationREACTOMER-HSA-167169
Formation of the HIV-1 Early Elongation ComplexREACTOMER-HSA-167158
Tat-mediated elongation of the HIV-1 transcriptREACTOMER-HSA-167246
Formation of HIV-1 elongation complex containing HIV-1 TatREACTOMER-HSA-167200
Formation of HIV elongation complex in the absence of HIV TatREACTOMER-HSA-167152
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Transcriptional Regulation by TP53REACTOMER-HSA-3700989
RNA Polymerase I, RNA Polymerase III, and Mitochondrial TranscriptionREACTOMER-HSA-504046
RNA Polymerase I TranscriptionREACTOMER-HSA-73864
RNA Polymerase I Promoter ClearanceREACTOMER-HSA-73854
RNA Polymerase I Transcription InitiationREACTOMER-HSA-73762
RNA Polymerase I Promoter EscapeREACTOMER-HSA-73772
RNA Polymerase I Chain ElongationREACTOMER-HSA-73777
RNA Polymerase I Transcription TerminationREACTOMER-HSA-73863
RNA Polymerase II TranscriptionREACTOMER-HSA-73857
RNA Polymerase II Pre-transcription EventsREACTOMER-HSA-674695
RNA Polymerase II Transcription Pre-Initiation And Promoter OpeningREACTOMER-HSA-73779
RNA Polymerase II Transcription Initiation And Promoter ClearanceREACTOMER-HSA-76042
RNA Polymerase II Transcription InitiationREACTOMER-HSA-75953
RNA Polymerase II Promoter EscapeREACTOMER-HSA-73776
RNA Pol II CTD phosphorylation and interaction with CEREACTOMER-HSA-77075
RNA Polymerase II Transcription ElongationREACTOMER-HSA-75955
Formation of the Early Elongation ComplexREACTOMER-HSA-113418
Formation of RNA Pol II elongation complexREACTOMER-HSA-112382
mRNA CappingREACTOMER-HSA-72086
Epigenetic regulation of gene expressionREACTOMER-HSA-212165
Negative epigenetic regulation of rRNA expressionREACTOMER-HSA-5250941
NoRC negatively regulates rRNA expressionREACTOMER-HSA-427413
MetabolismREACTOMER-HSA-1430728
Cytosolic iron-sulfur cluster assemblyREACTOMER-HSA-2564830
DNA RepairREACTOMER-HSA-73894
Nucleotide Excision RepairREACTOMER-HSA-5696398
Global Genome Nucleotide Excision Repair (GG-NER)REACTOMER-HSA-5696399
Formation of Incision Complex in GG-NERREACTOMER-HSA-5696395
Dual Incision in GG-NERREACTOMER-HSA-5696400
Transcription-Coupled Nucleotide Excision Repair (TC-NER)REACTOMER-HSA-6781827
Formation of TC-NER Pre-Incision ComplexREACTOMER-HSA-6781823
Dual incision in TC-NERREACTOMER-HSA-6782135
Gap-filling DNA repair synthesis and ligation in TC-NERREACTOMER-HSA-6782210
TP53 Regulates Transcription of DNA Repair GenesREACTOMER-HSA-6796648

Protein levels (Protein atlas)

Not detected
Low
Medium
High
cerebral cortex
cerebellum
hippocampus
caudate
thyroid gland
parathyroid gland
adrenal gland
nasopharynx
bronchus
lung
oral mucosa
salivary gland
esophagus
stomach 1
stomach 2
duodenum
small intestine
colon
rectum
liver
gallbladder
pancreas
kidney
urinary bladder
testis
epididymis
seminal vesicle
prostate
vagina
ovary
fallopian tube
endometrium 1
endometrium 2
cervix, uterine
placenta
breast
heart muscle
smooth muscle
skeletal muscle
soft tissue 1
soft tissue 2
adipose tissue
skin 1
skin 2
appendix
spleen
lymph node
tonsil
bone marrow

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA128406956fluorouracilChemicalClinicalAnnotation, VariantAnnotationambiguousPD18267032, 20078613, 20385995, 28796378
PA131285527oxaliplatinChemicalClinicalAnnotation, VariantAnnotationassociatedPD18267032, 19434073, 20078613, 20385995, 21449681, 22026922, 22188361, 29662106
PA150595617platinumChemicalClinicalAnnotationassociatedPD19434073, 21449681, 22026922, 22188361, 29662106
PA164713176Platinum compoundsChemicalClinicalAnnotation, VariantAnnotationambiguousPD18347182, 19434073, 21449681, 22026922, 22188361, 23962907, 24446315, 25069034, 25592234, 27498158, 27995989, 28796378, 29662106
PA166122986radiotherapyChemicalVariantAnnotationnot associatedPD28796378
PA166123026progression-free survivalDiseaseVariantAnnotationassociatedPD
PA166124223pneumonitisDiseaseClinicalAnnotationassociatedPD25069034
PA166151827adverse eventsDiseaseClinicalAnnotationassociatedPD27498158
PA443314AlopeciaDiseaseClinicalAnnotationassociatedPD
PA443340AnemiaDiseaseClinicalAnnotationassociatedPD
PA443560Breast NeoplasmsDiseaseClinicalAnnotationassociatedPD25495407
PA443622Carcinoma, Non-Small-Cell LungDiseaseClinicalAnnotationassociatedPD24446315, 25069034, 27498158
PA444101Esophageal NeoplasmsDiseaseClinicalAnnotationassociatedPD19434073, 21449681, 22026922, 22188361, 29662106
PA444773LeukopeniaDiseaseClinicalAnnotationassociatedPD
PA444937MesotheliomaDiseaseClinicalAnnotationassociatedPD
PA445062NeoplasmsDiseaseClinicalAnnotationassociatedPD18347182, 22026922, 22188361, 23962907, 24446315, 25592234, 27995989, 29662106
PA445204Ovarian NeoplasmsDiseaseClinicalAnnotationassociatedPD19434073, 21449681, 22026922, 22188361, 29662106
PA445218Pancreatic NeoplasmsDiseaseClinicalAnnotationassociatedPD19434073, 21449681, 22026922, 22188361, 29662106
PA445601OsteosarcomaDiseaseClinicalAnnotationassociatedPD19434073, 21449681, 22026922, 22188361, 29662106
PA445742Stomach NeoplasmsDiseaseVariantAnnotationnot associatedPD28796378
PA445828Testicular NeoplasmsDiseaseClinicalAnnotationassociatedPD
PA446108Colorectal NeoplasmsDiseaseClinicalAnnotation, VariantAnnotationassociatedPD18267032, 19434073, 20078613, 20385995, 21449681, 22026922, 22188361, 29662106
PA448645bleomycinChemicalClinicalAnnotationassociatedPD
PA449014cisplatinChemicalClinicalAnnotationassociatedPD19434073, 21449681, 22026922, 22188361, 29662106
PA449383docetaxelChemicalClinicalAnnotationassociatedPD25495407
PA449552etoposideChemicalClinicalAnnotationassociatedPD
PA449748gemcitabineChemicalClinicalAnnotationassociatedPD
PA450198leucovorinChemicalClinicalAnnotation, VariantAnnotationassociatedPD18267032, 20078613, 20385995

References

Pubmed IDYearTitleCitations
371408132024KIAA1549 promotes the development and chemoresistance of colorectal cancer by upregulating ERCC2.0
382857842024Genetic Polymorphisms of XPC, XPD, XPG Genes and their Association with Radiotherapy Induced Toxicity among Head and Neck Cancer Patients: A Hospital Based Study from Maharashtra.0
371408132024KIAA1549 promotes the development and chemoresistance of colorectal cancer by upregulating ERCC2.0
382857842024Genetic Polymorphisms of XPC, XPD, XPG Genes and their Association with Radiotherapy Induced Toxicity among Head and Neck Cancer Patients: A Hospital Based Study from Maharashtra.0
363084302023TFIIH mutations can impact on translational fidelity of the ribosome.1
365944752023Involvement of ERCC1 (rs3212986) and ERCC2 (rs1799793, rs13181) polymorphisms of DNA repair genes in breast cancer occurrence in Burkina Faso.2
368932742023A disease-associated XPA allele interferes with TFIIH binding and primarily affects transcription-coupled nucleotide excision repair.2
370766182023Lesion recognition by XPC, TFIIH and XPA in DNA excision repair.10
374980632023NOP2-mediated m5C methylation of XPD is associated with hepatocellular carcinoma progression.8
379338612023Differing structures and dynamics of two photolesions portray verification differences by the human XPD helicase.2
363084302023TFIIH mutations can impact on translational fidelity of the ribosome.1
365944752023Involvement of ERCC1 (rs3212986) and ERCC2 (rs1799793, rs13181) polymorphisms of DNA repair genes in breast cancer occurrence in Burkina Faso.2
368932742023A disease-associated XPA allele interferes with TFIIH binding and primarily affects transcription-coupled nucleotide excision repair.2
370766182023Lesion recognition by XPC, TFIIH and XPA in DNA excision repair.10
374980632023NOP2-mediated m5C methylation of XPD is associated with hepatocellular carcinoma progression.8

Citation

Anne Stary ; Alain Sarasin

ERCC2 (Excision repair cross-complementing rodent repair deficiency, complementation group 2)

Atlas Genet Cytogenet Oncol Haematol. 2001-02-01

Online version: http://atlasgeneticsoncology.org/gene/297/ercc2