XRCC6 (X-ray repair complementing defective repair in Chinese hamster cells 6)

2010-06-01   Sabina Pucci , Maria Josç Zonetti 

Lab of Molecular Pathology, Dept of Biopathology, University of Rome Tor Vergata, Via Montpellier, 00133 Rome, Italy





The KU70 gene is composed of 13 exons.


2156 bp mRNA.



The Ku70 protein is 609 amino acid long and its molecular weight is 69.8 kDa. It is composed of 3 domains: an amino (N) amino-terminal alpha/beta domain, a central beta-barrel domain and a helical C-terminal arm (Rivera-Calzada et al., 2007). The C-terminal region consists of a 5 kDa SAP domain (Ku70-SAP) which involved in DNA binding during NHEJ reaction.
Atlas Image


Ku70 is ubiquitously expressed. Changes in Ku70 expression correlated to a pathological state.


Ku was originally reported to be a nuclear protein, consistent with its functions as a subunit 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). Recently, it has been demonstrated that the shift from the nucleus to the cytoplasm of the Ku70/Ku80 proteins in tumor cells could represents a mechanism to inhibit cell death through the Ku70-Bax-sCLU interactions, giving rise to a new chemoresistant clone with a more aggressive phenotype.


Ku is a heterodimeric protein composed of two subunits with molecular weight of 70 and 86 kDa. Ku forms a complex with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to form the full DNA-dependent protein kinase, DNA-PK, consisting of 470 kDa and required for the non-homologous end joining (NHEJ) pathway of DNA repair. The Ku heterodimer binds the ends of various types of DNA discontinuity, and is involved in the repair of DNA breaks caused by an incorrect DNA replication, V(D)J recombination, physiological oxidations, ionizing irradiation, and some chemotherapeutic drug effects (Featherstone and Jackson, 1999). The principal role of Ku proteins is to take care of the homeostasis of the genome being involved in telomere maintenance, specific gene transcription, DNA replication, cell-cycle regulation and regulation of apoptosis induction. Ku70 has been shown to bind to the pro-apoptotic protein BAX in the cytoplasm in normal, undamaged cell. After DNA damage inducing DNA double-strand breaks repair (UV treatment, ionizing radiation, etc.) Ku70 allows the translocation of Bax to the mitochondria leading to the release of death-promoting factors, such as cytochrome c, in the cytoplasmic compartment. In normal cells, after an irreversible cell damage, nCLU cooperates with Ku70 to induce apoptotic death, activating the translocation of Bax to mitochondria whereas the sCLU protein stabilizes the Ku70-Bax interaction in the cytoplasm acting as cytoprotectant. The Ku70-Bax-sCLU interaction in the cytoplasm seems to play an important role in cell survival pathways and in cell death escape, that in pathological condition could lead to the survival of the aberrant cell clone. Overall, the dynamic interactions among CLU, Ku70, and Bax seems to have an important role in both tumor insurgence and its progression (Pucci et al., 2009a; Pucci et al., 2009b).
Atlas Image
Ku70/80-CLU-Bax interactions. (A) Bax is localized inactive in the cytoplasm in normal, undamaged cell interacting with the Ku70 protein C-terminus. 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).

Implicated in

Entity name
Colon cancer
The colon cancer expression and the localization of Ku70 and Ku80 are related to tumor progression in colon cancer. DNA repair is inhibited in high infiltrative colon carcinoma by Ku80 loss and Ku70 cell compartment shift (from the nucleus to the cytoplasm).
Moreover in colorectal carcinoma was demonstrated a very important role of Ku70 expression, localization, and physical interaction with CLU and Bax. In fact the Ku70-CLU-Bax colocalization in the cytoplasm and an increase in Ku70-CLU-Bax binding were observed in highly aggressive human colon cancer (Pucci et al., 2004; Pucci et al., 2009c), confirming that these interactions regulate the Bax-dependent cell death.
Atlas Image
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 Ku86 was positive in the nuclei of control tissues (normal mucosa). Nuclear Ku86 expression was strongly decreased in node-negative tumors (pT3N0). No staining for Ku86 was found in the nucleus or in the cytoplasm of node-positive carcinomas (pT3N1).
Atlas Image
Ku70-Bax-CLU pathological interaction. Apoptosis escaping. The shift of clusterin forms production, the loss of Ku80, and the cytoplasmic relocalization of Ku70 are related to cell death inhibition and cancer progression.
Entity name
Breast cancer
Experimental data further reported an inactivation of Ku DNA-binding activity, essential for genomic stability in breast and in bladder carcinomas. A dysfunction of this protective activity let the aberrant cell clone growing. In highly infiltrative and metastatic tumors of the breast and bladder, the impaired DNA-repair activity is due to the loss of Ku86 (Pucci et al., 2001) and to the Ku70 shifting from the nucleus to the cytoplasm. The shift from the nucleus to the cytoplasm of the Ku70/80 proteins in tumor cells could represents a mechanism to inhibit cell death through the cooperative interaction with sCLU, giving rise to a new chemoresistant clone with a more aggressive phenotype.


Pubmed IDLast YearTitleAuthors
103779441999Ku, a DNA repair protein with multiple cellular functions?Featherstone C et al
198794222009CLU and colon cancer. The dual face of CLU: from normal to malignant phenotype.Mazzarelli P et al
22120141990Cell surface expression of the 70-kD component of Ku, a DNA-binding nuclear autoantigen.Prabhakar BS et al
196231702009Clusterin in stool: a new biomarker for colon cancer screening?Pucci S et al
191770102009Interleukin-6 affects cell death escaping mechanisms acting on Bax-Ku70-Clusterin interactions in human colon cancer progression.Pucci S et al
171599212007Structural model of full-length human Ku70-Ku80 heterodimer and its recognition of DNA and DNA-PKcs.Rivera-Calzada A et al

Other Information

Locus ID:

NCBI: 2547
MIM: 152690
HGNC: 4055
Ensembl: ENSG00000196419


dbSNP: 2547
ClinVar: 2547
TCGA: ENSG00000196419


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Non-homologous end-joiningKEGGko03450
Non-homologous end-joiningKEGGhsa03450
DNA-PK complexKEGGhsa_M00297
DNA-PK complexKEGGM00297
Infectious diseaseREACTOMER-HSA-5663205
HIV InfectionREACTOMER-HSA-162906
HIV Life CycleREACTOMER-HSA-162587
Early Phase of HIV Life CycleREACTOMER-HSA-162594
Integration of provirusREACTOMER-HSA-162592
2-LTR circle formationREACTOMER-HSA-164843
Immune SystemREACTOMER-HSA-168256
Innate Immune SystemREACTOMER-HSA-168249
Cytosolic sensors of pathogen-associated DNAREACTOMER-HSA-1834949
STING mediated induction of host immune responsesREACTOMER-HSA-1834941
IRF3-mediated induction of type I IFNREACTOMER-HSA-3270619
DNA Double-Strand Break RepairREACTOMER-HSA-5693532
Nonhomologous End-Joining (NHEJ)REACTOMER-HSA-5693571
Neutrophil degranulationREACTOMER-HSA-6798695

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
171241662006Dynamic assembly of end-joining complexes requires interaction between Ku70/80 and XRCC4.139
205389112010Ku70 corrupts DNA repair in the absence of the Fanconi anemia pathway.124
173342242007SIRT1 promotes DNA repair activity and deacetylation of Ku70.111
167135812006Three-dimensional structure of the human DNA-PKcs/Ku70/Ku80 complex assembled on DNA and its implications for DNA DSB repair.100
203831232010Ku is a 5'-dRP/AP lyase that excises nucleotide damage near broken ends.93
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
213986142011Cutting edge: Ku70 is a novel cytosolic DNA sensor that induces type III rather than type I IFN.78
191341202009Rickettsial outer-membrane protein B (rOmpB) mediates bacterial invasion through Ku70 in an actin, c-Cbl, clathrin and caveolin 2-dependent manner.70
183031132008Transcriptome sequencing of malignant pleural mesothelioma tumors.65
191163882009A field synopsis on low-penetrance variants in DNA repair genes and cancer susceptibility.63


Sabina Pucci ; Maria Josç Zonetti

XRCC6 (X-ray repair complementing defective repair in Chinese hamster cells 6)

Atlas Genet Cytogenet Oncol Haematol. 2010-06-01

Online version: http://atlasgeneticsoncology.org/gene/246/xrcc6-(x-ray-repair-complementing-defective-repair-in-chinese-hamster-cells-6)