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XRCC3 (X-ray repair complementing defective repair in Chinese hamster cells 3)

Identity

HGNC (Hugo) XRCC3
LocusID (NCBI) 7517
Location 14q32.33
Location_base_pair Starts at 104163954 and ends at 104181823 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

Description 17 800 bp, 9 exons
Transcription 2,504 bp

Protein

Description 346 amino acids
Function XRCC3 is required for efficient repair of double strand breaks via homologous recombinational repair (link), for correct chromosomal segregation and for repair of DNA cross links. Inactivation of XRCC3 in CHO cells results in increased radiation and cisplatin sensitivity. In human cells, XRCC3 forms a complex with Rad51C which is recruited early to DNA damage. Inactivation of XRCC3 in human cells leads to a two-fold sensitivity to DNA cross-linking agents, impaired Rad51 focus formation, elevated chromosome aberrations and five to seven-fold increased endoreduplication.
Homology XRCC3 is a paralog to rad51

Implicated in

Entity No human disease has been linked to inactivation of XRCC3. However, polymorphisms in XRCC3 may be associated with increased cancer risk (see below).
Note Genetic Epidemiology:
The most frequent polymorphism in XRCC3 is XRCC3 C18067T which results in a Thr to Met amino acid substitution at codon 241. Carriers of the variant T-allele of XRCC3 T241M have higher DNA adduct levels in lymphocyte DNA compared to homozygous C-allele carriers, indicating that the polymorphism is associated with lowered DNA repair capacity. The variant allele of XRCC3 T241M polymorphism has been associated with increased risk of squamous cell carcinoma of the head and neck in one study while another study found no association. No association has previously been found with colon cancer, non-melanoma skin cancer, prostate cancer, gastric cancer, ovarian cancer. Conflicting results have been published on the association with breast cancer, bladder cancer, malignant melanoma and lung cancer.
Two frequent SNP are upstream of XRCC3 T241M have also been studied, namely XRCC3 A4541G and XRCC3 A17897G. Neither polymorphism gives rise to amino acid changes. The variant allele of A17897G has been associated with decreased risk of breast cancer and ovarian cancer. The same tendency, but no significant associations was found for lung cancer.
XRCC3 A4541G was not associated to risk of breast cancer or lung cancer. However, homozygote carriers of the variant allele had lower risk of serous epithelial ovarian cancer.
  

External links

Nomenclature
HGNC (Hugo)XRCC3   12830
Cards
AtlasXRCC3ID335ch14q32
Entrez_Gene (NCBI)XRCC3  7517  X-ray repair complementing defective repair in Chinese hamster cells 3
GeneCards (Weizmann)XRCC3
Ensembl hg19 (Hinxton)ENSG00000126215 [Gene_View]  chr14:104163954-104181823 [Contig_View]  XRCC3 [Vega]
Ensembl hg38 (Hinxton)ENSG00000126215 [Gene_View]  chr14:104163954-104181823 [Contig_View]  XRCC3 [Vega]
ICGC DataPortalENSG00000126215
cBioPortalXRCC3
AceView (NCBI)XRCC3
Genatlas (Paris)XRCC3
WikiGenes7517
SOURCE (Princeton)XRCC3
Genomic and cartography
GoldenPath hg19 (UCSC)XRCC3  -     chr14:104163954-104181823 -  14q32.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)XRCC3  -     14q32.3   [Description]    (hg38-Dec_2013)
EnsemblXRCC3 - 14q32.3 [CytoView hg19]  XRCC3 - 14q32.3 [CytoView hg38]
Mapping of homologs : NCBIXRCC3 [Mapview hg19]  XRCC3 [Mapview hg38]
OMIM114480   600675   613972   
Gene and transcription
Genbank (Entrez)AF035586 AK022829 AK023646 AK124498 AK126706
RefSeq transcript (Entrez)NM_001100118 NM_001100119 NM_005432
RefSeq genomic (Entrez)AC_000146 NC_000014 NC_018925 NG_011516 NT_026437 NW_001838115 NW_004929393
Consensus coding sequences : CCDS (NCBI)XRCC3
Cluster EST : UnigeneHs.733412 [ NCBI ]
CGAP (NCI)Hs.733412
Alternative Splicing : Fast-db (Paris)GSHG0009645
Alternative Splicing GalleryENSG00000126215
Gene ExpressionXRCC3 [ NCBI-GEO ]     XRCC3 [ SEEK ]   XRCC3 [ MEM ]
SOURCE (Princeton)Expression in : [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO43542 (Uniprot)
NextProtO43542  [Medical]
With graphics : InterProO43542
Splice isoforms : SwissVarO43542 (Swissvar)
Domaine pattern : Prosite (Expaxy)RECA_2 (PS50162)   
Domains : Interpro (EBI)DNA_recomb/repair_Rad51_C    DNA_recomb/repair_RecA-like    P-loop_NTPase    RecA_ATP-bd   
Related proteins : CluSTrO43542
Domain families : Pfam (Sanger)Rad51 (PF08423)   
Domain families : Pfam (NCBI)pfam08423   
DMDM Disease mutations7517
Blocks (Seattle)O43542
Human Protein AtlasENSG00000126215
Peptide AtlasO43542
HPRD07201
IPIIPI00023073   IPI01025002   IPI01025120   IPI01025078   IPI01024699   IPI01024861   IPI01025448   IPI01025987   
Protein Interaction databases
DIP (DOE-UCLA)O43542
IntAct (EBI)O43542
FunCoupENSG00000126215
BioGRIDXRCC3
IntegromeDBXRCC3
STRING (EMBL)XRCC3
Ontologies - Pathways
QuickGOO43542
Ontology : AmiGOfour-way junction DNA binding  double-strand break repair via homologous recombination  DNA catabolic process, endonucleolytic  protein binding  ATP binding  nucleus  replication fork  cytoplasm  mitochondrion  ATP catabolic process  DNA repair  DNA recombination  cellular response to DNA damage stimulus  DNA-dependent ATPase activity  crossover junction endodeoxyribonuclease activity  response to organic substance  regulation of centrosome duplication  Rad51C-XRCC3 complex  perinuclear region of cytoplasm  resolution of mitotic recombination intermediates  positive regulation of mitotic cell cycle spindle assembly checkpoint  
Ontology : EGO-EBIfour-way junction DNA binding  double-strand break repair via homologous recombination  DNA catabolic process, endonucleolytic  protein binding  ATP binding  nucleus  replication fork  cytoplasm  mitochondrion  ATP catabolic process  DNA repair  DNA recombination  cellular response to DNA damage stimulus  DNA-dependent ATPase activity  crossover junction endodeoxyribonuclease activity  response to organic substance  regulation of centrosome duplication  Rad51C-XRCC3 complex  perinuclear region of cytoplasm  resolution of mitotic recombination intermediates  positive regulation of mitotic cell cycle spindle assembly checkpoint  
Pathways : KEGGHomologous recombination   
Protein Interaction DatabaseXRCC3
DoCM (Curated mutations)XRCC3
Wikipedia pathwaysXRCC3
Gene fusion - rearrangements
Polymorphisms : SNP, variants
NCBI Variation ViewerXRCC3 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)XRCC3
dbVarXRCC3
ClinVarXRCC3
1000_GenomesXRCC3 
Exome Variant ServerXRCC3
SNP (GeneSNP Utah)XRCC3
SNP : HGBaseXRCC3
Genetic variants : HAPMAPXRCC3
Genomic VariantsXRCC3  XRCC3 [DGVbeta]
Mutations
ICGC Data PortalENSG00000126215 
Somatic Mutations in Cancer : COSMICXRCC3 
CONAN: Copy Number AnalysisXRCC3 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)14:104163954-104181823
Mutations and Diseases : HGMDXRCC3
OMIM114480    600675    613972   
MedgenXRCC3
NextProtO43542 [Medical]
GENETestsXRCC3
Disease Genetic AssociationXRCC3
Huge Navigator XRCC3 [HugePedia]  XRCC3 [HugeCancerGEM]
snp3D : Map Gene to Disease7517
DGIdb (Drug Gene Interaction db)XRCC3
General knowledge
Homologs : HomoloGeneXRCC3
Homology/Alignments : Family Browser (UCSC)XRCC3
Phylogenetic Trees/Animal Genes : TreeFamXRCC3
Chemical/Protein Interactions : CTD7517
Chemical/Pharm GKB GenePA37422
Clinical trialXRCC3
Cancer Resource (Charite)ENSG00000126215
Other databases
Probes
Litterature
PubMed367 Pubmed reference(s) in Entrez
CoreMineXRCC3
GoPubMedXRCC3
iHOPXRCC3

Bibliography

XRCC2 and XRCC3, new human Rad51-family members, promote chromosome stability and protect against DNA cross-links and other damages.
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Mammalian recombination-repair genes XRCC2 and XRCC3 promote correct chromosome segregation.
Griffin CS, Simpson PJ, Wilson CR, Thacker J
Nature cell biology. 2000 ; 2 (10) : 757-761.
PMID 11025669
 
A variant within the DNA repair gene XRCC3 is associated with the development of melanoma skin cancer.
Winsey SL, Haldar NA, Marsh HP, Bunce M, Marshall SE, Harris AL, Wojnarowska F, Welsh KI
Cancer research. 2000 ; 60 (20) : 5612-5616.
PMID 11059748
 
No association between the XPD (Lys751G1n) polymorphism or the XRCC3 (Thr241Met) polymorphism and lung cancer risk.
David-Beabes GL, Lunn RM, London SJ
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2001 ; 10 (8) : 911-912.
PMID 11489761
 
DNA repair gene polymorphisms, bulky DNA adducts in white blood cells and bladder cancer in a case-control study.
Matullo G, Guarrera S, Carturan S, Peluso M, Malaveille C, Davico L, Piazza A, Vineis P
International journal of cancer. Journal international du cancer. 2001 ; 92 (4) : 562-567.
PMID 11304692
 
XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample of healthy subjects.
Matullo G, Palli D, Peluso M, Guarrera S, Carturan S, Celentano E, Krogh V, Munnia A, Tumino R, Polidoro S, Piazza A, Vineis P
Carcinogenesis. 2001 ; 22 (9) : 1437-1445.
PMID 11532866
 
DNA repair gene XRCC3 241Met variant is not associated with risk of cutaneous malignant melanoma.
Duan Z, Shen H, Lee JE, Gershenwald JE, Ross MI, Mansfield PF, Duvic M, Strom SS, Spitz MR, Wei Q
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2002 ; 11 (10 Pt 1) : 1142-1143.
PMID 12376526
 
Variants in DNA double-strand break repair genes and breast cancer susceptibility.
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A variant of the DNA repair gene XRCC3 and risk of squamous cell carcinoma of the head and neck: a case-control analysis.
Shen H, Sturgis EM, Dahlstrom KR, Zheng Y, Spitz MR, Wei Q
International journal of cancer. Journal international du cancer. 2002 ; 99 (6) : 869-872.
PMID 12115490
 
DNA repair gene XRCC3 codon 241 polymorphism, its interaction with smoking and XRCC1 polymorphisms, and bladder cancer risk.
Stern MC, Umbach DM, Lunn RM, Taylor JA
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2002 ; 11 (9) : 939-943.
PMID 12223443
 
Polymorphisms in DNA double-strand break repair genes and breast cancer risk in the Nurses' Health Study.
Han J, Hankinson SE, Ranu H, De Vivo I, Hunter DJ
Carcinogenesis. 2004 ; 25 (2) : 189-195.
PMID 14578164
 
No association between the DNA repair gene XRCC3 T241M polymorphism and risk of skin cancer and breast cancer.
Jacobsen NR, Nexˆ˝ BA, Olsen A, Overvad K, Wallin H, Tjˆ˝nneland A, Vogel U
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2003 ; 12 (6) : 584-585.
PMID 12815008
 
Lack of involvement of nucleotide excision repair gene polymorphisms in colorectal cancer.
Mort R, Mo L, McEwan C, Melton DW
British journal of cancer. 2003 ; 89 (2) : 333-337.
PMID 12865926
 
Polymorphisms in DNA repair and metabolic genes in bladder cancer.
Sanyal S, Festa F, Sakano S, Zhang Z, Steineck G, Norming U, Wijkstrˆm H, Larsson P, Kumar R, Hemminki K
Carcinogenesis. 2004 ; 25 (5) : 729-734.
PMID 14688016
 
Polymorphisms of the DNA repair genes XRCC1, XRCC3, XPD, interaction with environmental exposures, and bladder cancer risk in a case-control study in northern Italy.
Shen M, Hung RJ, Brennan P, Malaveille C, Donato F, Placidi D, Carta A, Hautefeuille A, Boffetta P, Porru S
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2003 ; 12 (11 Pt 1) : 1234-1240.
PMID 14652287
 
Polymorphisms of XRCC1 and XRCC3 genes and susceptibility to breast cancer.
Smith TR, Miller MS, Lohman K, Lange EM, Case LD, Mohrenweiser HW, Hu JJ
Cancer letters. 2003 ; 190 (2) : 183-190.
PMID 12565173
 
Xrcc3 is recruited to DNA double strand breaks early and independent of Rad51.
Forget AL, Bennett BT, Knight KL
Journal of cellular biochemistry. 2004 ; 93 (3) : 429-436.
PMID 15372620
 
XRCC3 polymorphisms and risk of lung cancer.
Jacobsen NR, Raaschou-Nielsen O, Nexˆ˝ B, Wallin H, Overvad K, Tjˆ˝nneland A, Vogel U
Cancer letters. 2004 ; 213 (1) : 67-72.
PMID 15312685
 
Specific combinations of DNA repair gene variants and increased risk for non-small cell lung cancer.
Popanda O, Schattenberg T, Phong CT, Butkiewicz D, Risch A, Edler L, Kayser K, Dienemann H, Schulz V, Drings P, Bartsch H, Schmezer P
Carcinogenesis. 2004 ; 25 (12) : 2433-2441.
PMID 15333465
 
XRCC3 deficiency results in a defect in recombination and increased endoreduplication in human cells.
Yoshihara T, Ishida M, Kinomura A, Katsura M, Tsuruga T, Tashiro S, Asahara T, Miyagawa K
The EMBO journal. 2004 ; 23 (3) : 670-680.
PMID 14749735
 
Polymorphisms in DNA repair genes and epithelial ovarian cancer risk.
Auranen A, Song H, Waterfall C, Dicioccio RA, Kuschel B, Kjaer SK, Hogdall E, Hogdall C, Stratton J, Whittemore AS, Easton DF, Ponder BA, Novik KL, Dunning AM, Gayther S, Pharoah PD
International journal of cancer. Journal international du cancer. 2005 ; 117 (4) : 611-618.
PMID 15924337
 
Basal cell carcinoma and variants in genes coding for immune response, DNA repair, folate and iron metabolism.
Festa F, Kumar R, Sanyal S, UndˆŠn B, Nordfors L, Lindholm B, Snellman E, Schalling M, Fˆrsti A, Hemminki K
Mutation research. 2005 ; 574 (1-2) : 105-111.
PMID 15914210
 
Selected DNA repair polymorphisms and gastric cancer in Poland.
Huang WY, Chow WH, Rothman N, Lissowska J, Llaca V, Yeager M, Zatonski W, Hayes RB
Carcinogenesis. 2005 ; 26 (8) : 1354-1359.
PMID 15802298
 
Selected genetic polymorphisms in MGMT, XRCC1, XPD, and XRCC3 and risk of head and neck cancer: a pooled analysis.
Huang WY, Olshan AF, Schwartz SM, Berndt SI, Chen C, Llaca V, Chanock SJ, Fraumeni JF Jr, Hayes RB
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2005 ; 14 (7) : 1747-1753.
PMID 16030112
 
A comparison of response to cisplatin, radiation and combined treatment for cells deficient in recombination repair pathways.
Raaphorst GP, Leblanc M, Li LF
Anticancer research. 2005 ; 25 (1A) : 53-58.
PMID 15816518
 
Genetic variants of DNA repair genes and prostate cancer: a population-based study.
Ritchey JD, Huang WY, Chokkalingam AP, Gao YT, Deng J, Levine P, Stanczyk FZ, Hsing AW
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PMID 16030105
 
Double-strand break repair gene polymorphisms and risk of breast or ovarian cancer.
Webb PM, Hopper JL, Newman B, Chen X, Kelemen L, Giles GG, Southey MC, Chenevix-Trench G, Spurdle AB
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2005 ; 14 (2) : 319-323.
PMID 15734952
 
Polymorphisms of the XRCC1, XRCC3, & XPD genes, and colorectal cancer risk: a case-control study in Taiwan.
Yeh CC, Sung FC, Tang R, Chang-Chieh CR, Hsieh LL
BMC cancer. 2005 ; 5 : page 12.
PMID 15679883
 
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Contributor(s)

Written11-2005Ulla Vogel
National Research Centre for the Working Environment, Lersř Parkalle 105, DK-2100 Copenhagen O, Denmark

Citation

This paper should be referenced as such :
Vogel, U
XRCC3 (X-ray repair complementing defective repair in Chinese hamster cells 3)
Atlas Genet Cytogenet Oncol Haematol. 2006;10(2):105-106.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/XRCC3ID335ch14q32.html

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