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

Identity

HGNC	ERCC1
Location	19q13.32

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	ERCC1   3433
Entrez_Gene	ERCC1  2067  excision repair cross-complementing rodent repair deficiency, complementation group 1 (includes overlapping antisense sequence)
	Cards
Atlas	ERCC1ID40481ch19q13
GeneCards	ERCC1
Ensembl	ERCC1 [Search_View]   ENSG00000012061 [Gene_View]
Genatlas	ERCC1
GeneLynx	ERCC1
eGenome	ERCC1
euGene	2067
	Genomic and cartography
GoldenPath	ERCC1  -  19q13.32   chr19:50604712-50619017 -  19q13.32   [Description]    (hg18-Mar_2006)
Ensembl	ERCC1 - 19q13.32 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	ERCC1
	Gene and transcription
Genbank	AA761510 [ ENTREZ ]
Genbank	AB069681 [ ENTREZ ]
Genbank	AF001925 [ ENTREZ ]
Genbank	AF433652 [ ENTREZ ]
Genbank	AK092039 [ ENTREZ ]
RefSeq	NM_001983 [ SRS ]    NM_001983 [ ENTREZ ]
RefSeq	NM_202001 [ SRS ]    NM_202001 [ ENTREZ ]
RefSeq	AC_000062 [ SRS ]    AC_000062 [ ENTREZ ]
RefSeq	AC_000151 [ SRS ]    AC_000151 [ ENTREZ ]
RefSeq	NC_000019 [ SRS ]    NC_000019 [ ENTREZ ]
RefSeq	NT_011109 [ SRS ]    NT_011109 [ ENTREZ ]
RefSeq	NW_001838496 [ SRS ]    NW_001838496 [ ENTREZ ]
RefSeq	NW_927217 [ SRS ]    NW_927217 [ ENTREZ ]
AceView	ERCC1 AceView - NCBI
Unigene	Hs.435981 [ SRS ]    Hs.435981 [ NCBI ]     HS435981 [ spliceNest ]
Fast-db	13380 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P07992 [ SRS]    P07992 [ EXPASY ]     P07992 [ INTERPRO ]     P07992 [ UNIPROT ]
Interpro	IPR000445 HhH [ SRS ]    IPR000445 HhH [ EBI ]
Interpro	IPR003583 HHH1_bd [ SRS ]    IPR003583 HHH1_bd [ EBI ]
Interpro	IPR004579 Rad10 [ SRS ]    IPR004579 Rad10 [ EBI ]
CluSTr	P07992
Pfam	PF00633 HHH [ SRS ]    PF00633 HHH [ Sanger ]    pfam00633 [ NCBI-CDD ]
Pfam	PF03834 Rad10 [ SRS ]    PF03834 Rad10 [ Sanger ]    pfam03834 [ NCBI-CDD ]
Smart	SM00278 HhH1 [EMBL]
Blocks	P07992
PDB	1Z00 [ SRS ]    1Z00 [ PdbSum ],   1Z00 [ IMB ]   1Z00 [ RSDB ]
PDB	2A1I [ SRS ]    2A1I [ PdbSum ],   2A1I [ IMB ]   2A1I [ RSDB ]
PDB	2A1J [ SRS ]    2A1J [ PdbSum ],   2A1J [ IMB ]   2A1J [ RSDB ]
PDB	2JNW [ SRS ]    2JNW [ PdbSum ],   2JNW [ IMB ]   2JNW [ RSDB ]
PDB	2JPD [ SRS ]    2JPD [ PdbSum ],   2JPD [ IMB ]   2JPD [ RSDB ]
HPRD	00533
	Protein Interaction databases
DIP	P07992
IntAct	P07992
	Polymorphism : SNP, mutations, diseases
OMIM	126380;610758    [ map ]
GENECLINICS	126380;610758
SNP	ERCC1 [dbSNP-NCBI]
SNP	NM_001983 [SNP-NCI]
SNP	NM_202001 [SNP-NCI]
SNP	ERCC1 [GeneSNPs - Utah]  ERCC1] [HGBASE - SRS]
HAPMAP	ERCC1 [HAPMAP]
COSMIC	ERCC1 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	ERCC1
	General knowledge
Family Browser	ERCC1 [UCSC Family Browser]
SOURCE	NM_001983
SOURCE	NM_202001
SMD	Hs.435981
SAGE	Hs.435981
GO	single-stranded DNA specific endodeoxyribonuclease activity [Amigo]  single-stranded DNA specific endodeoxyribonuclease activity
GO	nucleotide-excision repair complex [Amigo]  nucleotide-excision repair complex
GO	nucleotide-excision repair, DNA damage removal [Amigo]  nucleotide-excision repair, DNA damage removal
GO	nuclear chromosome, telomeric region [Amigo]  nuclear chromosome, telomeric region
GO	damaged DNA binding [Amigo]  damaged DNA binding
GO	damaged DNA binding [Amigo]  damaged DNA binding
GO	single-stranded DNA binding [Amigo]  single-stranded DNA binding
GO	endonuclease activity [Amigo]  endonuclease activity
GO	intracellular [Amigo]  intracellular
GO	nucleus [Amigo]  nucleus
GO	nucleoplasm [Amigo]  nucleoplasm
GO	DNA repair [Amigo]  DNA repair
GO	nucleotide-excision repair, DNA incision, 3'-to lesion [Amigo]  nucleotide-excision repair, DNA incision, 3'-to lesion
GO	nucleotide-excision repair, DNA incision, 5'-to lesion [Amigo]  nucleotide-excision repair, DNA incision, 5'-to lesion
GO	mitotic recombination [Amigo]  mitotic recombination
GO	response to oxidative stress [Amigo]  response to oxidative stress
GO	protein C-terminus binding [Amigo]  protein C-terminus binding
GO	hydrolase activity [Amigo]  hydrolase activity
GO	protein domain specific binding [Amigo]  protein domain specific binding
GO	negative regulation of telomere maintenance [Amigo]  negative regulation of telomere maintenance
GO	sequence-specific DNA binding [Amigo]  sequence-specific DNA binding
PubGene	ERCC1
TreeFam	ERCC1
CTD	2067 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	ERCC1 Related clones (RZPD - Berlin)
	PubMed
PubMed	137 Pubmed reference(s) in LocusLink

Bibliography

Correction of a nucleotide-excision-repair mutation by human chromosome 19 in hamster-human hybrid cells.

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PMID 3919454

ERCC1 and ERCC2 expression in malignant tissues from ovarian cancer patients.

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PMID 7678143

Messenger RNA levels of XPAC and ERCC1 in ovarian cancer tissue correlate with response to platinum-based chemotherapy.

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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.

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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.

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PMID 7559382

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PMID 8797573

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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.

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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.

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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)

Written	12-2006	Ulla 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

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Aug 11 21:13:37 2008