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ERCC1 (excision repair complementing defective repair in Chinese hamster.)

Identity

HGNC (Hugo) ERCC1
LocusID (NCBI) 2067
Location 19q13.32
Location_base_pair Starts at 45910591 and ends at 45927177 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

Description 14 305 bp and 10 exons
Transcription 1,101 bps

Protein

Description 297 amino acids
Expression ERCC1 is expressed at higher levels in tumor tissue compared to normal tissue and the expression shows more inter-individual variation among cancer patients than among healthy individuals. ERCC1 expression and ERCC1 protein levels in tumor tissue may predict response to chemotherapy. Thus, non-small cell lung cancer patients with undetectable ERCC1 protein levels in tumor tissue had a longer survival after cisplatin-based adjuvant chemotherapy than patients with detectable ERCC1 protein levels. However, high ERCC1 protein levels were associated with increased survival among patients who were not treated with chemotherapy).
Function ERCC1 was originally identified as a gene that complemented a certain DNA repair defective Chinese Hamster Ovary cells (CHO) UV20. ERCC1 forms a heterodimer with XPF (also called ERCC4) to form the endonuclease which makes the 5¹ incision during nucleotide excision repair.

ERCC1 mRNA levels in lymphocytes correlate positively with DNA repair capacity measured by host cell reactivation. ERCC1 mRNA levels correlate closely with XPD, OGG1 and RAI mRNA levels in lymphocytes.

In case-control studies of lung cancer patients, lung cancer patients were shown to have lower mRNA levels and lower DNA repair capacity than healthy controls. This was also found in a case-control study of head and neck cancer. However, in a prospective study of lung cancer, persons, who were later diagnosed with lung cancer did not have a lower ERCC1 mRNA level than those who did not get lung cancer, indicating that the low ERCC1 expression level observed in cancer patients may be a result of the disease rather than a cause.

ERCC1 expression seems to be inducible at least at the mRNA level. Thus, the expression of ERCC1 in human lymphocytes correlated with increased solar influx indicating that UV irradiation may induce ERCC1 expression. In mice, X-ray irradiation lead to increased ERCC1 expression in lung tissue, and ingestion of diesel exhaust particles increased ERCC1 expression in liver. This indicates that ERCC1 expression is inducible, and thus that ERCC1 expression levels may rather be a biomarker of the internal dose of DNA damage than a biomarker of DNA repair capacity or a mix of the two.

Mutations

Note One of the most frequently studied polymorphisms in ERCC1 is ERCC1 Asn118Asn (rs11615). Homozygous carriers of the haplotype ERCC1 Asn118AsnA, ASE-1 G-21AG, PPP1R13L IVS1 A4364GA have been shown to be at increased risk of breast cancer and lung cancer.
The ERCC1 Asn118Asn polymorphism was found not to correlate with mRNA levels.
ERCC1 C8092A (rs3212986) was found to interact with smoking in relation to risk of lung cancer in a large case-control study. ERCC1 C8092A was found not to correlate with mRNA levels in peripheral blood cells.

Implicated in

Entity Breast cancer
Prognosis Thus, women who were homozygous carriers of the haplotype had a 9.5-fold higher risk of breast cancer before 55 years of age than women who were not homozygous carriers. Older women and heterozygous carriers were not at an increased risk of breast cancer.
  
Entity Lung cancer
Disease Homozygous carriers of the haplotype were found to be at 4.9-fold increased risk of lung cancer in the age interval 50-55 years. The association was stronger among women than among men, although the difference was not statistically significant. In subsequent study including more cases and a larger comparison group, a statistically significant difference between genders was found. Furthermore, it was found that the haplotype interacts with smoking intensity. Thus, among women, who were carriers of the haplotype, additional smoking at high smoking intensity (>20 cigarettes/day) was associated with increased lung cancer risk. This was not seen among women who were not homozygous carriers of the haplotype or among men.

The haplotype was not associated with risk of testis cancer or with risk of colorectal adenomas or colorectal cancer. Furthermore, the haplotype was not associated with risk of basal cell carcinoma among older persons (>60 years).These results indicate that the haplotype may be associated with risk of cancer primarily among young and middle aged persons and that it may be specific for women.

  
Entity Leukemia and bladder cancer
Disease The variant allele of ERCC1 Asn118Asn has also been combined with the polymorphisms XPD Asp312Asn and XPD Lys752Gln in haplotype analysis. Here, the haplotype GAT was associated with increased risk of leukemia and bladder cancer among non-smokers and the ACC haplotype was associated with lowered risk of bladder cancer.
  
Entity Colorectal cancer, small cell lung cancer, and non small cell lung cancer
Disease Carriers of the variant allele of ERCC1 Asn118Asn were found to have a worse prognosis of colorectal cancer, small cell lung cancer and non-small cell lung cancer, whereas no association with risk of colorectal cancer has been found.
  

External links

Nomenclature
HGNC (Hugo)ERCC1   3433
Cards
AtlasERCC1ID40481ch19q13
Entrez_Gene (NCBI)ERCC1  2067  excision repair cross-complementing rodent repair deficiency, complementation group 1 (includes overlapping antisense sequence)
GeneCards (Weizmann)ERCC1
Ensembl (Hinxton)ENSG00000012061 [Gene_View]  chr19:45910591-45927177 [Contig_View]  ERCC1 [Vega]
AceView (NCBI)ERCC1
Genatlas (Paris)ERCC1
WikiGenes2067
SOURCE (Princeton)NM_001166049 NM_001983 NM_202001
Genomic and cartography
GoldenPath (UCSC)ERCC1  -  19q13.32   chr19:45910591-45927177 -  19q13.32   [Description]    (hg19-Feb_2009)
EnsemblERCC1 - 19q13.32 [CytoView]
Mapping of homologs : NCBIERCC1 [Mapview]
OMIM126380   610758   
Gene and transcription
Genbank (Entrez)AA761510 AB069681 AF001925 AF433652 AK092039
RefSeq transcript (Entrez)NM_001166049 NM_001983 NM_202001
RefSeq genomic (Entrez)AC_000151 NC_000019 NC_018930 NG_015839 NT_011109 NW_001838496 NW_004929415
Consensus coding sequences : CCDS (NCBI)ERCC1
Cluster EST : UnigeneHs.435981 [ NCBI ]
CGAP (NCI)Hs.435981
Alternative Splicing : Fast-db (Paris)GSHG0015913
Alternative Splicing GalleryENSG00000012061
Gene ExpressionERCC1 [ NCBI-GEO ]     ERCC1 [ SEEK ]   ERCC1 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP07992 (Uniprot)
NextProtP07992  [Medical]
With graphics : InterProP07992
Splice isoforms : SwissVarP07992 (Swissvar)
Domains : Interpro (EBI)DNA_repair_Rad10    HhH_motif    Hlx-hairpin-Hlx_DNA-bd_motif    Restrct_endonuc-II-like    RuvA_2-like   
Related proteins : CluSTrP07992
Domain families : Pfam (Sanger)HHH (PF00633)    Rad10 (PF03834)   
Domain families : Pfam (NCBI)pfam00633    pfam03834   
Domain families : Smart (EMBL)HhH1 (SM00278)  
Domain structure : Prodom (Prabi Lyon)DNA_repair_Rad10 (PD013585)   
DMDM Disease mutations2067
Blocks (Seattle)P07992
PDB (SRS)1Z00    2A1I    2A1J    2JNW    2JPD   
PDB (PDBSum)1Z00    2A1I    2A1J    2JNW    2JPD   
PDB (IMB)1Z00    2A1I    2A1J    2JNW    2JPD   
PDB (RSDB)1Z00    2A1I    2A1J    2JNW    2JPD   
Human Protein AtlasENSG00000012061
Peptide AtlasP07992
HPRD00533
IPIIPI00014040   IPI00640338   IPI01014834   IPI00045494   IPI00401902   
Protein Interaction databases
DIP (DOE-UCLA)P07992
IntAct (EBI)P07992
FunCoupENSG00000012061
BioGRIDERCC1
InParanoidP07992
Interologous Interaction database P07992
IntegromeDBERCC1
STRING (EMBL)ERCC1
Ontologies - Pathways
Ontology : AmiGOsingle-stranded DNA endodeoxyribonuclease activity  nucleotide-excision repair complex  nucleotide-excision repair, DNA damage removal  pyrimidine dimer repair by nucleotide-excision repair  nuclear chromosome, telomeric region  TFIID-class transcription factor binding  replicative cell aging  damaged DNA binding  single-stranded DNA binding  protein binding  nucleus  nucleoplasm  transcription factor TFIID complex  nucleolus  cytoplasm  DNA repair  transcription-coupled nucleotide-excision repair  nucleotide-excision repair  nucleotide-excision repair  nucleotide-excision repair  nucleotide-excision repair, DNA incision, 3'-to lesion  nucleotide-excision repair, DNA incision, 5'-to lesion  double-strand break repair  DNA recombination  mitotic recombination  syncytium formation  response to oxidative stress  germ cell development  spermatogenesis  response to nutrient  protein C-terminus binding  cell proliferation  male gonad development  UV protection  response to sucrose  response to X-ray  multicellular organismal aging  TBP-class protein binding  protein domain specific binding  negative regulation of telomere maintenance  post-embryonic hemopoiesis  multicellular organism growth  negative regulation of apoptotic process  structure-specific DNA binding  isotype switching  oogenesis  embryonic organ development  chromosome organization  
Ontology : EGO-EBIsingle-stranded DNA endodeoxyribonuclease activity  nucleotide-excision repair complex  nucleotide-excision repair, DNA damage removal  pyrimidine dimer repair by nucleotide-excision repair  nuclear chromosome, telomeric region  TFIID-class transcription factor binding  replicative cell aging  damaged DNA binding  single-stranded DNA binding  protein binding  nucleus  nucleoplasm  transcription factor TFIID complex  nucleolus  cytoplasm  DNA repair  transcription-coupled nucleotide-excision repair  nucleotide-excision repair  nucleotide-excision repair  nucleotide-excision repair  nucleotide-excision repair, DNA incision, 3'-to lesion  nucleotide-excision repair, DNA incision, 5'-to lesion  double-strand break repair  DNA recombination  mitotic recombination  syncytium formation  response to oxidative stress  germ cell development  spermatogenesis  response to nutrient  protein C-terminus binding  cell proliferation  male gonad development  UV protection  response to sucrose  response to X-ray  multicellular organismal aging  TBP-class protein binding  protein domain specific binding  negative regulation of telomere maintenance  post-embryonic hemopoiesis  multicellular organism growth  negative regulation of apoptotic process  structure-specific DNA binding  isotype switching  oogenesis  embryonic organ development  chromosome organization  
Pathways : KEGGNucleotide excision repair    Fanconi anemia pathway   
REACTOMEERCC1
Protein Interaction DatabaseERCC1
Wikipedia pathwaysERCC1
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)ERCC1
SNP (GeneSNP Utah)ERCC1
SNP : HGBaseERCC1
Genetic variants : HAPMAPERCC1
1000_GenomesERCC1 
ICGC programENSG00000012061 
Somatic Mutations in Cancer : COSMICERCC1 
CONAN: Copy Number AnalysisERCC1 
Mutations and Diseases : HGMDERCC1
OMIM126380    610758   
GENETestsERCC1
Disease Genetic AssociationERCC1
Huge Navigator ERCC1 [HugePedia]  ERCC1 [HugeCancerGEM]
Genomic VariantsERCC1  ERCC1 [DGVbeta]
Exome VariantERCC1
dbVarERCC1
ClinVarERCC1
snp3D : Map Gene to Disease2067
General knowledge
Homologs : HomoloGeneERCC1
Homology/Alignments : Family Browser (UCSC)ERCC1
Phylogenetic Trees/Animal Genes : TreeFamERCC1
Chemical/Protein Interactions : CTD2067
Chemical/Pharm GKB GenePA155
Clinical trialERCC1
Cancer Resource (Charite)ENSG00000012061
Other databases
Probes
Litterature
PubMed426 Pubmed reference(s) in Entrez
CoreMineERCC1
iHOPERCC1

Bibliography

Correction of a nucleotide-excision-repair mutation by human chromosome 19 in hamster-human hybrid cells.
Thompson LH, Mooney CL, Burkhart-Schultz K, Carrano AV, Siciliano MJ
Somatic cell and molecular genetics. 1985 ; 11 (1) : 87-92.
PMID 3919454
 
ERCC1 and ERCC2 expression in malignant tissues from ovarian cancer patients.
Dabholkar M, Bostick-Bruton F, Weber C, Bohr VA, Egwuagu C, Reed E
Journal of the National Cancer Institute. 1992 ; 84 (19) : 1512-1517.
PMID 1433335
 
Expression of excision repair genes in non-malignant bone marrow from cancer patients.
Dabholkar M, Bostick-Bruton F, Weber C, Egwuagu C, Bohr VA, Reed E
Mutation research. 1993 ; 293 (2) : 151-160.
PMID 7678143
 
Messenger RNA levels of XPAC and ERCC1 in ovarian cancer tissue correlate with response to platinum-based chemotherapy.
Dabholkar M, Vionnet J, Bostick-Bruton F, Yu JJ, Reed E
The Journal of clinical investigation. 1994 ; 94 (2) : 703-708.
PMID 8040325
 
Human DNA repair excision nuclease. Analysis of the roles of the subunits involved in dual incisions by using anti-XPG and anti-ERCC1 antibodies.
Matsunaga T, Mu D, Park CH, Reardon JT, Sancar A
The Journal of biological chemistry. 1995 ; 270 (35) : 20862-20869.
PMID 7657672
 
Purification and characterization of the XPF-ERCC1 complex of human DNA repair excision nuclease.
Park CH, Bessho T, Matsunaga T, Sancar A
The Journal of biological chemistry. 1995 ; 270 (39) : 22657-22660.
PMID 7559382
 
Reduced DNA repair capacity in lung cancer patients.
Wei Q, Cheng L, Hong WK, Spitz MR
Cancer research. 1996 ; 56 (18) : 4103-4107.
PMID 8797573
 
Reduced expression levels of nucleotide excision repair genes in lung cancer: a case-control analysis.
Cheng L, Spitz MR, Hong WK, Wei Q
Carcinogenesis. 2000 ; 21 (8) : 1527-1530.
PMID 10910954
 
DNA repair capacity: inconsistency between effect of over-expression of five NER genes and the correlation to mRNA levels in primary lymphocytes.
Vogel U, Dybdahl M, Frentz G, Nexo BA
Mutation research. 2000 ; 461 (3) : 197-210.
PMID 11056291
 
Inter-individual variation, seasonal variation and close correlation of OGG1 and ERCC1 mRNA levels in full blood from healthy volunteers.
Vogel U, Mˆ½ller P, Dragsted L, Loft S, Pedersen A, Sandstrˆm B
Carcinogenesis. 2002 ; 23 (9) : 1505-1509.
PMID 12189194
 
DNA adduct formation and oxidative stress in colon and liver of Big Blue rats after dietary exposure to diesel particles.
Dybdahl M, Risom L, Mˆ½ller P, Autrup H, Wallin H, Vogel U, Bornholdt J, Daneshvar B, Dragsted LO, Weimann A, Poulsen HE, Loft S
Carcinogenesis. 2003 ; 24 (11) : 1759-1766.
PMID 12919963
 
A specific haplotype of single nucleotide polymorphisms on chromosome 19q13.2-3 encompassing the gene RAI is indicative of post-menopausal breast cancer before age 55.
Nexˆ½ BA, Vogel U, Olsen A, Ketelsen T, Bukowy Z, Thomsen BL, Wallin H, Overvad K, Tjˆ½nneland A
Carcinogenesis. 2003 ; 24 (5) : 899-904.
PMID 12771034
 
ERCC1 gene polymorphism as a predictor for clinical outcome in advanced colorectal cancer patients treated with platinum-based chemotherapy.
Park DJ, Zhang W, Stoehlmacher J, Tsao-Wei D, Groshen S, Gil J, Yun J, Sones E, Mallik N, Lenz HJ
Clinical advances in hematology & oncology : H&O. 2003 ; 1 (3) : 162-166.
PMID 16224397
 
Oxidative DNA damage and defence gene expression in the mouse lung after short-term exposure to diesel exhaust particles by inhalation.
Risom L, Dybdahl M, Bornholdt J, Vogel U, Wallin H, Mˆ½ller P, Loft S
Carcinogenesis. 2003 ; 24 (11) : 1847-1852.
PMID 12919962
 
Single nucleotide polymorphisms and outcome in docetaxel-cisplatin-treated advanced non-small-cell lung cancer.
Isla D, Sarries C, Rosell R, Alonso G, Domine M, Taron M, Lopez-Vivanco G, Camps C, Botia M, Nuˆ±ez L, Sanchez-Ronco M, Sanchez JJ, Lopez-Brea M, Barneto I, Paredes A, Medina B, Artal A, Lianes P
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2004 ; 15 (8) : 1194-1203.
PMID 15277258
 
Association between polymorphisms of ERCC1 and XPD and survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy.
Ryu JS, Hong YC, Han HS, Lee JE, Kim S, Park YM, Kim YC, Hwang TS
Lung cancer (Amsterdam, Netherlands). 2004 ; 44 (3) : 311-316.
PMID 15140544
 
Two regions in chromosome 19q13.2-3 are associated with risk of lung cancer.
Vogel U, Laros I, Jacobsen NR, Thomsen BL, Bak H, Olsen A, Bukowy Z, Wallin H, Overvad K, Tjˆ½nneland A, Nexˆ½ BA, Raaschou-Nielsen O
Mutation research. 2004 ; 546 (1-2) : 65-74.
PMID 14757194
 
Polymorphisms in RAI and in genes of nucleotide and base excision repair are not associated with risk of testicular cancer.
Laska MJ, Nexˆ½ BA, Vistisen K, Poulsen HE, Loft S, Vogel U
Cancer letters. 2005 ; 225 (2) : 245-251.
PMID 15885892
 
Polymorphisms/haplotypes in DNA repair genes and smoking: a bladder cancer case-control study.
Matullo G, Guarrera S, Sacerdote C, Polidoro S, Davico L, Gamberini S, Karagas M, Casetta G, Rolle L, Piazza A, Vineis P
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2005 ; 14 (11 Pt 1) : 2569-2578.
PMID 16284380
 
Effect of polymorphisms in XPD, RAI, ASE-1 and ERCC1 on the risk of basal cell carcinoma among Caucasians after age 50.
Vogel U, Olsen A, Wallin H, Overvad K, Tjˆ½nneland A, Nexˆ½ BA
Cancer detection and prevention. 2005 ; 29 (3) : 209-214.
PMID 15936590
 
Gene-smoking interaction associations for the ERCC1 polymorphisms in the risk of lung cancer.
Zhou W, Liu G, Park S, Wang Z, Wain JC, Lynch TJ, Su L, Christiani DC
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2005 ; 14 (2) : 491-496.
PMID 15734977
 
DNA repair polymorphisms and cancer risk in non-smokers in a cohort study.
Matullo G, Dunning AM, Guarrera S, Baynes C, Polidoro S, Garte S, Autrup H, Malaveille C, Peluso M, Airoldi L, Veglia F, Gormally E, Hoek G, Krzyzanowski M, Overvad K, Raaschou-Nielsen O, Clavel-Chapelon F, Linseisen J, Boeing H, Trichopoulou A, Palli D, Krogh V, Tumino R, Panico S, Bueno-De-Mesquita HB, Peeters PH, Lund E, Pera G, Martinez C, Dorronsoro M, Barricarte A, Tormo MJ, Quiros JR, Day NE, Key TJ, Saracci R, Kaaks R, Riboli E, Vineis P
Carcinogenesis. 2006 ; 27 (5) : 997-1007.
PMID 16308313
 
Polymorphisms in genes of nucleotide and base excision repair: risk and prognosis of colorectal cancer.
Moreno V, Gemignani F, Landi S, Gioia-Patricola L, Chabrier A, Blanco I, Gonzˆ°lez S, Guino E, CapellˆÝ G, Canzian F
Clinical cancer research : an official journal of the American Association for Cancer Research. 2006 ; 12 (7 Pt 1) : 2101-2108.
PMID 16609022
 
DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy.
Olaussen KA, Dunant A, Fouret P, Brambilla E, Andrˆ© F, Haddad V, Taranchon E, Filipits M, Pirker R, Popper HH, Stahel R, Sabatier L, Pignon JP, Tursz T, Le Chevalier T, IALT Bio Investigators, Soria JC
The New England journal of medicine. 2006 ; 355 (10) : 983-991.
PMID 16957145
 
Increased mRNA expression levels of ERCC1, OGG1 and RAI in colorectal adenomas and carcinomas.
Saebˆ½ M, Skjelbred CF, Nexˆ½ BA, Wallin H, Hansteen IL, Vogel U, Kure EH
BMC cancer. 2006 ; 6 : page 208.
PMID 16914027
 
Effects of polymorphisms in ERCC1, ASE-1 and RAI on the risk of colorectal carcinomas and adenomas: a case control study.
Skjelbred CF, Saebˆ½ M, Nexˆ½ BA, Wallin H, Hansteen IL, Vogel U, Kure EH
BMC cancer. 2006 ; 6 : page 175.
PMID 16817948
 
ERCC1, XPD and RAI mRNA levels in lymphocytes are not associated with lung cancer risk in a prospective study of Danes.
Vogel U, Nexˆ½ BA, Tjˆ½nneland A, Wallin H, Hertel O, Raaschou-Nielsen O
Mutation research. 2006 ; 593 (1-2) : 88-96.
PMID 16054657
 
Gene-environment interactions between smoking and a haplotype of RAI, ASE-1 and ERCC1 polymorphisms among women in relation to risk of lung cancer in a population-based study.
Vogel U, Sˆ½rensen M, Hansen RD, Tjˆ½nneland A, Overvad K, Wallin H, Nexˆ½ BA, Raaschou-Nielsen O
Cancer letters. 2007 ; 247 (1) : 159-165.
PMID 16690207
 
Effects of ERCC1 expression in peripheral blood on the risk of head and neck cancer.
Yang M, Kim WH, Choi Y, Lee SH, Kim KR, Lee HS, Tae K
European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP). 2006 ; 15 (3) : 269-273.
PMID 16679872
 
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Contributor(s)

Written12-2006Ulla Vogel

Citation

This paper should be referenced as such :
Vogel U . ERCC1 (excision repair complementing defective repair in Chinese hamster.). Atlas Genet Cytogenet Oncol Haematol. December 2006 .
URL : http://AtlasGeneticsOncology.org/Genes/ERCC1ID40481ch19q13.html

The various updated versions of this paper are referenced and archived by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/38403/1/12-2006-ERCC1ID40481ch19q13.pdf   [ Bibliographic record ]

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indexed on : Fri Apr 18 17:27:13 CEST 2014

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