The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

XRCC6  -  X-ray repair complementing defective...

Homo sapiens

Synonyms: 5'-dRP lyase Ku70, 5'-deoxyribose-5-phosphate lyase Ku70, 70 kDa subunit of Ku antigen, ATP-dependent DNA helicase 2 subunit 1, ATP-dependent DNA helicase II 70 kDa subunit, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of XRCC6


Psychiatry related information on XRCC6

  • Measurements of regional or local cerebral blood flow (CBF) by the xenon-133 inhalation method and stable xenon computerized tomography CBF (CTCBF) method were made during relaxed wakefulness and different stages of REM and non-REM sleep in normal age-matched volunteers, narcoleptics, and sleep apneics [6].

High impact information on XRCC6

  • Bacterial invasion is dependent on the presence of cholesterol-enriched microdomains containing Ku70 [5].
  • Moreover, we show that irradiated cells deficient for Ku70 are incapable of targeting Mre11 to subnuclear foci that may represent DNA-repair complexes [7].
  • Nevertheless, Ku70 and Mre11 were differentially expressed during meiosis [7].
  • In early meiotic prophase, however, when meiotic recombination is most probably initiated, Mre11 was abundant, whereas Ku70 was not detectable [7].
  • Ku70 and Ku80 share a common topology and form a dyad-symmetrical molecule with a preformed ring that encircles duplex DNA [8].

Chemical compound and disease context of XRCC6


Biological context of XRCC6

  • The common promoter region of the human collagen type IV genes COL4A1 and COL4A2 comprises a C5TC7 sequence ('CTC box') which is specifically recognized by the recently identified transcription factor CTC box binding factor (CTCBF) involved in the control of divergent transcription of the two genes [11].
  • Nuclear clusterin/XIP8, an x-ray-induced Ku70-binding protein that signals cell death [12].
  • Overexpression of nuclear CLU/XIP8 or its minimal Ku70 binding domain (120 aa of CLU/XIP8 C terminus) in nonirradiated MCF-7:WS8 cells dramatically reduced cell growth and colony-forming ability concomitant with increased G(1) cell cycle checkpoint arrest and increased cell death [12].
  • Our data suggest that Ku can affect the susceptibility to anticancer drug-induced apoptosis [13].
  • Ku70 is one component of a protein complex, the Ku70/Ku80 heterodimer, which binds to DNA double-strand breaks and activates DNA-dependent protein kinase (DNA-PK), leading to DNA damage repair [14].

Anatomical context of XRCC6

  • Here we show that the IR repair, DNA end binding and DNA-PK defects in Ku70-/- embryonic stem cells can be counteracted by introducing epitope-tagged wild-type Ku70 cDNA [15].
  • Interestingly, YY1 interacts with Ku70 and Ku80 in HeLa cells [16].
  • Ku-null mutant cell lines Ku70-/- and Ku80-/- were highly sensitive to anticancer drugs, compared with their wild-type cells [13].
  • Accordingly, in resting human IgM+IgD+ B cells, HoxC4, Oct-1, and Ku70/Ku86 can be readily identified as bound to the Igamma and Iepsilon promoters but not the Ialpha1/Ialpha2 promoters [17].
  • We found that tumour-transformed tissue shows positive immunostaining of DNA-PKcs, Ku86 and Ku70, while non-neoplastic squamous epithelium and tumour-free cervix glands show negative immunoreactivity [18].

Associations of XRCC6 with chemical compounds

  • We find that Ku70 is phosphorylated at a single serine residue, serine 6, located in the putative transcriptional activation domain, and Ku80 is phosphorylated at serines 577 and 580 and at threonine 715 [19].
  • Western blot analysis demonstrated that celecoxib downregulated the expression of Ku70 protein and inhibited the kinase activity of DNA-PKcs, which are involved in the double-stranded DNA-break repair machinery [20].
  • A detailed examination of the involvement of the DNA repair pathway following Vorinostat treatment showed that Vorinostat reduced the expression of the repair-related genes Ku70, Ku80, and Rad50 in A375 cells as detected by Western blot analysis [21].
  • By using glutathione S-transferase fusion proteins derived from Ku-70 and coimmunoprecipitation experiments with lysates prepared from human thymocytes and Jurkat and UT7 cells, we show that Vav associates with Ku-70 [22].
  • A proline-to-leucine mutation in the carboxy SH3 of Vav that blocks interaction with proline-rich sequences does not modify the binding of Ku-70, which lacks this motif [22].

Physical interactions of XRCC6

  • First, using various WRN deletion mutants we show that 50 amino acids at the amino terminus are required and sufficient to interact with Ku70/80 [23].
  • Recently we have demonstrated that Ku70 interacted with TRF2, a mammalian telomere-binding protein [24].
  • The Ku70 autoantigen interacts with p40phox in B lymphocytes [25].
  • In vitro translated Ku70 interacted with HSF1 by binding to and displacing it from HSE [26].
  • CONCLUSION: The candidates, poly(ADP-ribose)polymerase-1 (PARP-1) and the heterodimeric complex Ku70/Ku80, are known to participate in inflammatory disorders as well as tumorgenesis [27].

Co-localisations of XRCC6


Regulatory relationships of XRCC6

  • Moreover, we demonstrated that Ku70/80 strongly stimulates and alters WRN exonuclease activity [23].
  • Furthermore, electroporation of neutralizing anti-Ku70, Ku 80 and Ku70/80 antibodies into A549 cells totally suppressed IL-13 and IL-4-stimulated 15-LO-1 induction in these cells [29].
  • Junctions were repaired in the same manner in MO59K extracts in which accurate NHEJ was inactivated by inhibition of Ku70 or DNA-PK(cs) [30].

Other interactions of XRCC6


Analytical, diagnostic and therapeutic context of XRCC6


  1. Expression of Ku70 and Ku80 mediated by NF-kappa B and cyclooxygenase-2 is related to proliferation of human gastric cancer cells. Lim, J.W., Kim, H., Kim, K.H. J. Biol. Chem. (2002) [Pubmed]
  2. Identification and biochemical characterization of a Werner's syndrome protein complex with Ku70/80 and poly(ADP-ribose) polymerase-1. Li, B., Navarro, S., Kasahara, N., Comai, L. J. Biol. Chem. (2004) [Pubmed]
  3. Isolation of Ku70-binding proteins (KUBs). Yang, C.R., Yeh, S., Leskov, K., Odegaard, E., Hsu, H.L., Chang, C., Kinsella, T.J., Chen, D.J., Boothman, D.A. Nucleic Acids Res. (1999) [Pubmed]
  4. Expression and heterodimer-binding activity of Ku70 and Ku80 in human non-melanoma skin cancer. Parrella, P., Mazzarelli, P., Signori, E., Perrone, G., Marangi, G.F., Rabitti, C., Delfino, M., Prencipe, M., Gallo, A.P., Rinaldi, M., Fabbrocini, G., Delfino, S., Persichetti, P., Fazio, V.M. J. Clin. Pathol. (2006) [Pubmed]
  5. Ku70, a component of DNA-dependent protein kinase, is a mammalian receptor for Rickettsia conorii. Martinez, J.J., Seveau, S., Veiga, E., Matsuyama, S., Cossart, P. Cell (2005) [Pubmed]
  6. Cerebral blood flow in normal and abnormal sleep and dreaming. Meyer, J.S., Ishikawa, Y., Hata, T., Karacan, I. Brain and cognition. (1987) [Pubmed]
  7. Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis. Goedecke, W., Eijpe, M., Offenberg, H.H., van Aalderen, M., Heyting, C. Nat. Genet. (1999) [Pubmed]
  8. Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair. Walker, J.R., Corpina, R.A., Goldberg, J. Nature (2001) [Pubmed]
  9. Ku is a novel transcriptional recycling coactivator of the androgen receptor in prostate cancer cells. Mayeur, G.L., Kung, W.J., Martinez, A., Izumiya, C., Chen, D.J., Kung, H.J. J. Biol. Chem. (2005) [Pubmed]
  10. Ectopic expression of Bcl-XL or Ku70 protects human colon cancer cells (SW480) against curcumin-induced apoptosis while their down-regulation potentiates it. Rashmi, R., Kumar, S., Karunagaran, D. Carcinogenesis (2004) [Pubmed]
  11. Purification of the sequence-specific transcription factor CTCBF, involved in the control of human collagen IV genes: subunits with homology to Ku antigen. Genersch, E., Eckerskorn, C., Lottspeich, F., Herzog, C., Kühn, K., Pöschl, E. EMBO J. (1995) [Pubmed]
  12. Nuclear clusterin/XIP8, an x-ray-induced Ku70-binding protein that signals cell death. Yang, C.R., Leskov, K., Hosley-Eberlein, K., Criswell, T., Pink, J.J., Kinsella, T.J., Boothman, D.A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  13. Ku autoantigen affects the susceptibility to anticancer drugs. Kim, S.H., Kim, D., Han, J.S., Jeong, C.S., Chung, B.S., Kang, C.D., Li, G.C. Cancer Res. (1999) [Pubmed]
  14. Adenovirus-mediated expression of a dominant negative Ku70 fragment radiosensitizes human tumor cells under aerobic and hypoxic conditions. He, F., Li, L., Kim, D., Wen, B., Deng, X., Gutin, P.H., Ling, C.C., Li, G.C. Cancer Res. (2007) [Pubmed]
  15. Double-strand break repair by Ku70 requires heterodimerization with Ku80 and DNA binding functions. Jin, S., Weaver, D.T. EMBO J. (1997) [Pubmed]
  16. The Ku protein complex interacts with YY1, is up-regulated in human heart failure, and represses alpha myosin heavy-chain gene expression. Sucharov, C.C., Helmke, S.M., Langer, S.J., Perryman, M.B., Bristow, M., Leinwand, L. Mol. Cell. Biol. (2004) [Pubmed]
  17. Selective inhibition of class switching to IgG and IgE by recruitment of the HoxC4 and Oct-1 homeodomain proteins and Ku70/Ku86 to newly identified ATTT cis-elements. Schaffer, A., Kim, E.C., Wu, X., Zan, H., Testoni, L., Salamon, S., Cerutti, A., Casali, P. J. Biol. Chem. (2003) [Pubmed]
  18. Expression of DNA damage response proteins and complete remission after radiotherapy of stage IB-IIA of cervical cancer. Beskow, C., Kanter, L., Holgersson, A., Nilsson, B., Frankendal, B., Avall-Lundqvist, E., Lewensohn, R. Br. J. Cancer (2006) [Pubmed]
  19. DNA-dependent protein kinase phosphorylation sites in Ku 70/80 heterodimer. Chan, D.W., Ye, R., Veillette, C.J., Lees-Miller, S.P. Biochemistry (1999) [Pubmed]
  20. Inhibition of DNA repair as a mechanism of enhanced radioresponse of head and neck carcinoma cells by a selective cyclooxygenase-2 inhibitor, celecoxib. Raju, U., Ariga, H., Dittmann, K., Nakata, E., Ang, K.K., Milas, L. Int. J. Radiat. Oncol. Biol. Phys. (2005) [Pubmed]
  21. Vorinostat, a histone deacetylase inhibitor, enhances the response of human tumor cells to ionizing radiation through prolongation of gamma-H2AX foci. Munshi, A., Tanaka, T., Hobbs, M.L., Tucker, S.L., Richon, V.M., Meyn, R.E. Mol. Cancer Ther. (2006) [Pubmed]
  22. p95vav associates with the nuclear protein Ku-70. Romero, F., Dargemont, C., Pozo, F., Reeves, W.H., Camonis, J., Gisselbrecht, S., Fischer, S. Mol. Cell. Biol. (1996) [Pubmed]
  23. Requirements for the nucleolytic processing of DNA ends by the Werner syndrome protein-Ku70/80 complex. Li, B., Comai, L. J. Biol. Chem. (2001) [Pubmed]
  24. Human Ku70 interacts with heterochromatin protein 1alpha. Song, K., Jung, Y., Jung, D., Lee, I. J. Biol. Chem. (2001) [Pubmed]
  25. The Ku70 autoantigen interacts with p40phox in B lymphocytes. Grandvaux, N., Grizot, S., Vignais, P.V., Dagher, M.C. J. Cell. Sci. (1999) [Pubmed]
  26. Repression of the HSP70B promoter by NFIL6, Ku70, and MAPK involves three complementary mechanisms. Tang, D., Xie, Y., Zhao, M., Stevenson, M.A., Calderwood, S.K. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  27. Identification of poly(ADP-ribose)polymerase-1 and Ku70/Ku80 as transcriptional regulators of S100A9 gene expression. Grote, J., K??nig, S., Ackermann, D., Sopalla, C., Benedyk, M., Los, M., Kerkhoff, C. BMC Mol. Biol. (2006) [Pubmed]
  28. Interaction of human Ku70 with TRF2. Song, K., Jung, D., Jung, Y., Lee, S.G., Lee, I. FEBS Lett. (2000) [Pubmed]
  29. Ku autoantigen (DNA helicase) is required for interleukins-13/-4-induction of 15-lipoxygenase-1 gene expression in human epithelial cells. Kelavkar, U.P., Wang, S., Badr, K.F. Genes Immun. (2000) [Pubmed]
  30. DNA double strand break repair in human bladder cancer is error prone and involves microhomology-associated end-joining. Bentley, J., Diggle, C.P., Harnden, P., Knowles, M.A., Kiltie, A.E. Nucleic Acids Res. (2004) [Pubmed]
  31. Ku complex interacts with and stimulates the Werner protein. Cooper, M.P., Machwe, A., Orren, D.K., Brosh, R.M., Ramsden, D., Bohr, V.A. Genes Dev. (2000) [Pubmed]
  32. Ionizing radiation exposure results in up-regulation of Ku70 via a p53/ataxia-telangiectasia-mutated protein-dependent mechanism. Brown, K.D., Lataxes, T.A., Shangary, S., Mannino, J.L., Giardina, J.F., Chen, J., Baskaran, R. J. Biol. Chem. (2000) [Pubmed]
  33. Molecular cloning and sequencing of cDNAs encoding homologues of human Ku70 and Ku80 autoantigen from Xenopus and their expression in various Xenopus tissues. Yagura, T., Sumi, K. Biochim. Biophys. Acta (1999) [Pubmed]
WikiGenes - Universities