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XRCC5 (X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining))

Written2012-05Sabina Pucci, Tommaso Fisco , Maria José Zonetti
Lab. of Molecular Pathology, Dept. of Biopathology University of Rome Tor Vergata, Policlinico Tor Vergata, Viale Oxford, 00133 Rome, Italy

(Note : for Links provided by Atlas : click)


Alias_namesX-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining; Ku autoantigen, 80kD)
Alias_symbol (synonym)KU80
Other aliasKARP1
LocusID (NCBI) 7520
Atlas_Id 337
Location 2q35  [Link to chromosome band 2q35]
Location_base_pair Starts at 216109297 and ends at 216206293 bp from pter ( according to hg19-Feb_2009)  [Mapping XRCC5.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CEP95 (17q23.3) / XRCC5 (2q35)GIGYF2 (2q37.1) / XRCC5 (2q35)GSTP1 (11q13.2) / XRCC5 (2q35)
SERPINE2 (2q36.1) / XRCC5 (2q35)WDR7 (18q21.31) / XRCC5 (2q35)XRCC5 (2q35) / ACADL (2q34)
XRCC5 (2q35) / HTR2B (2q37.1)XRCC5 (2q35) / MYO5A (15q21.2)XRCC5 (2q35) / PTGR1 (9q31.3)


Description The Ku80 gene is composed of 21 exons. It belongs together with KU70 to the family of care taker genes.


Description Two isoforms of Ku80 encoded by the same genes, namely Ku80 and Karp-1 are expressed and function in primate cells.
Karp-1 has some biochemical properties, which resemble those of Ku80, and the function of Karp-1 could partially replace that of Ku80 in DSB repair (Koibe et al., 2011). However the role in the cells of this isoform is still unclear.
The Ku80 protein is 732 amino acid long and its molecular weight is 83 kDa. It is composed of 3 domains: an amino (N) terminal alpha/beta domain, a central beta-barrel domain and a helical-C terminal arm. The 19 kDa C-terminal region of Ku80 is implicated in the recruitment of DNA-PKcs by Ku to sites of damage (Rivera-Calzada et al., 2007). Moreover it belongs to the "Care Taker gene", detecting double strands breaks.
Expression Ku80 expression has been demonstrated in various cell types and its localization changes during the cell-cycle progression or with a pathological state.
Ku80 in addition to its well known regulatory functions in DNA repair, revealed to behave as a somatostatin receptor in gastric carcinoma cell (Le Romancer, 1994).
Localisation Ku was originally reported to be a nuclear protein, consistent with its function as a subunits of DNA- PK involved in DNA double strand breaks repair. However several studies have revealed the cytoplasmic or cell surface localization of ku proteins in various cell types (Prabhakar et al., 1990).
In highly infiltrative and metastatic tumors of the colon, breast and bladder, the impaired DNA-repair activity is due to the loss of Ku80 and to the Ku70 shifting from the nucleus to the cytoplasm (Pucci et al., 2001). This mechanism can be controlled by various external growth-regulating stimuli.
In normal cell Ku80 activation and translocation into nucleus could be regulated or stimulated by the induction of nuclear Clusterin (nClu)-Ku70 interactions. (Pucci et al., 2009a; Pucci et al., 2009b; Mazzarelli et al., 2009).
Function Ku80 is one component of a protein complex, the Ku70/80 heterodimer that can bind tightly to free DNA ends and activate the DNA-PKcs.
The principal role of Ku proteins is to take care of the homeostasis of the genome being involved in telomere maintenance, regulation of apoptosis induction, specific gene transcription, DNA replication and cell-cycle regulation. The function of this caretaker gene is to suppress chromosomal aberrations translocation and aneuploidy.
It has been demonstrated that Ku80 may act as a caretaker gene that maintains the integrity of the genoma by a mechanism involving the suppression of chromosomal rearrangements (Difilippantonio et al., 2000).
  A. Ku80 is localized in the nucleus in normal, undamaged cell interacting with the Ku70 protein. sCLU stabilizes the Ku70-Bax interaction in the cytoplasm acting as cytoprotectant. B. After DNA damage inducing DNA double-strand breaks repair (UV treatment, ionizing radiation, etc.) Ku70 allows the translocation of Bax to the mitochondria inducing apoptosis (Mazzarelli et al., 2009). C. The differential shift of clusterin isoform production, the loss of Ku80, and the cytoplasmic relocalization of Ku70 are related to cell death inhibition and cancer progression.

Implicated in

Entity Cancer insurgence and progression
Note The changes in Ku70 and Ku80 expression and localization are related to tumor progression. In normal cell they usually are placed in the nucleus, where they cooperate to repair double strands breaks that could occur during DNA replication. In breast, bladder, and colon cancers (Pucci et al., 2004a; Pucci et al., 2009c) DNA repair is inhibited in high infiltrative carcinomas through the loss of Ku80 and the Ku70 cell compartment shifting from nucleus to the cytoplasm. Ku70 shifts from the nucleus to the cytoplasm and binds, together with sCLU, Bax inhibiting its homodimerization and translocation to the mitochondria preventing apoptosis induction.
Somatostatin treatment to a colon carcinoma cell line (Caco-2) strongly modulates the activation of Ku70/80 heterodimer and the level of Ku80 in the nucleus by increasing its specific mRNA level (Pucci et al., 2004b). Ku80 could be a signal transducer and activator factor behaving as the intermediate of the SST transduction pathway by the internalization and the migration from the cell membrane to the nucleus.
Tumor-specific modulation of Ku70/80 in human colon cancer. Ku70 staining was strongly positive in the nuclei of normal mucosa. In node-negative carcinomas (pT3N0) Ku70 expression slightly decreased and it localized mainly in the nucleus. In node-positive carcinomas (pT3N1) Ku70 staining was distributed mainly in cytoplasm. The expression of Ku80 was positive in the nuclei of control tissues (normal mucosa). Nuclear Ku80 expression was strongly decreased in node-negative tumors (pT3N0). No staining for Ku80 was found in the nucleus or in the cytoplasm of node-positive carcinomas (pT3N1).


DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation.
Difilippantonio MJ, Zhu J, Chen HT, Meffre E, Nussenzweig MC, Max EE, Ried T, Nussenzweig A.
Nature. 2000 Mar 30;404(6777):510-4.
PMID 10761921
KARP-1 works as a heterodimer with Ku70, but the function of KARP-1 cannot perfectly replace that of Ku80 in DSB repair.
Koike M, Yutoku Y, Koike A.
Exp Cell Res. 2011 Oct 1;317(16):2267-75. Epub 2011 Jul 2.
PMID 21756904
The 86-kDa subunit of autoantigen Ku is a somatostatin receptor regulating protein phosphatase-2A activity.
Le Romancer M, Reyl-Desmars F, Cherifi Y, Pigeon C, Bottari S, Meyer O, Lewin MJ.
J Biol Chem. 1994 Jul 1;269(26):17464-8.
PMID 8021251
CLU and colon cancer. The dual face of CLU: from normal to malignant phenotype.
Mazzarelli P, Pucci S, Spagnoli LG.
Adv Cancer Res. 2009;105:45-61. (REVIEW)
PMID 19879422
Cell surface expression of the 70-kD component of Ku, a DNA-binding nuclear autoantigen.
Prabhakar BS, Allaway GP, Srinivasappa J, Notkins AL.
J Clin Invest. 1990 Oct;86(4):1301-5.
PMID 2212014
Clusterin in stool: a new biomarker for colon cancer screening?
Pucci S, Bonanno E, Sesti F, Mazzarelli P, Mauriello A, Ricci F, Zoccai GB, Rulli F, Galata G, Spagnoli LG.
Am J Gastroenterol. 2009a Nov;104(11):2807-15. Epub 2009 Jul 21.
PMID 19623170
CLU "in and out": looking for a link.
Pucci S, Mazzarelli P, Nucci C, Ricci F, Spagnoli LG.
Adv Cancer Res. 2009c;105:93-113. (REVIEW)
PMID 19879425
Structural model of full-length human Ku70-Ku80 heterodimer and its recognition of DNA and DNA-PKcs.
Rivera-Calzada A, Spagnolo L, Pearl LH, Llorca O.
EMBO Rep. 2007 Jan;8(1):56-62. Epub 2006 Dec 8.
PMID 17159921


This paper should be referenced as such :
Pucci, S ; Fisco, T ; Zonetti, MJ
XRCC5 (X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining))
Atlas Genet Cytogenet Oncol Haematol. 2012;16(11):844-847.
Free journal version : [ pdf ]   [ DOI ]
On line version :

External links

HGNC (Hugo)XRCC5   12833
Entrez_Gene (NCBI)XRCC5  7520  X-ray repair cross complementing 5
AliasesKARP-1; KARP1; KU80; KUB2; 
Ku86; NFIV
GeneCards (Weizmann)XRCC5
Ensembl hg19 (Hinxton)ENSG00000079246 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000079246 [Gene_View]  ENSG00000079246 [Sequence]  chr2:216109297-216206293 [Contig_View]  XRCC5 [Vega]
ICGC DataPortalENSG00000079246
TCGA cBioPortalXRCC5
Genatlas (Paris)XRCC5
SOURCE (Princeton)XRCC5
Genetics Home Reference (NIH)XRCC5
Genomic and cartography
GoldenPath hg38 (UCSC)XRCC5  -     chr2:216109297-216206293 +  2q35   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)XRCC5  -     2q35   [Description]    (hg19-Feb_2009)
GoldenPathXRCC5 - 2q35 [CytoView hg19]  XRCC5 - 2q35 [CytoView hg38]
Mapping of homologs : NCBIXRCC5 [Mapview hg19]  XRCC5 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AK026166 AK096408 AK222603 AK290740 BC019027
RefSeq transcript (Entrez)NM_021141
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)XRCC5
Alternative Splicing GalleryENSG00000079246
Gene ExpressionXRCC5 [ NCBI-GEO ]   XRCC5 [ EBI - ARRAY_EXPRESS ]   XRCC5 [ SEEK ]   XRCC5 [ MEM ]
Gene Expression Viewer (FireBrowse)XRCC5 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)7520
GTEX Portal (Tissue expression)XRCC5
Human Protein AtlasENSG00000079246-XRCC5 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)XRCC5
DMDM Disease mutations7520
Blocks (Seattle)XRCC5
Human Protein Atlas [tissue]ENSG00000079246-XRCC5 [tissue]
IPIIPI00220834   IPI00012911   IPI00871391   IPI00926445   
Protein Interaction databases
Ontologies - Pathways
Huge Navigator XRCC5 [HugePedia]
snp3D : Map Gene to Disease7520
BioCentury BCIQXRCC5
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD7520
Chemical/Pharm GKB GenePA37425
Clinical trialXRCC5
canSAR (ICR)XRCC5 (select the gene name)
DataMed IndexXRCC5
PubMed457 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Feb 7 14:01:48 CET 2020

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