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Gene Review

XRCC5  -  X-ray repair complementing defective...

Homo sapiens

Synonyms: 86 kDa subunit of Ku antigen, ATP-dependent DNA helicase 2 subunit 2, ATP-dependent DNA helicase II 80 kDa subunit, CTC box-binding factor 85 kDa subunit, CTC85, ...
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Disease relevance of XRCC5


Psychiatry related information on XRCC5

  • We investigated the psychological sequelae of incest through the use of the Draw-A-Person Questionnaire (DAPQ; Karp, 1990), a projective technique with an objective component [6].
  • First- and third-grade black children were administered Kagan's Matching Familiar Figures Test, Karp and Konstadt's Children's Embedded Figures Test (CEFT), and Shore, Milgram, and Malasky's Locus of Control Interview (LCI) [7].

High impact information on XRCC5

  • Ku70 and Ku80 share a common topology and form a dyad-symmetrical molecule with a preformed ring that encircles duplex DNA [8].
  • The discovery of homologues from the yeast Saccharomyces cerevisiae of the human Ku DNA-end-binding proteins (HDF1 and KU80) has established that this organism is capable of non-homologous double-strand end joining (NHEJ), a form of DNA double-strand break repair (DSBR) active in mammalian V(D)J recombination [9].
  • Ku80: product of the XRCC5 gene and its role in DNA repair and V(D)J recombination [10].
  • Three-dimensional structure of the human DNA-PKcs/Ku70/Ku80 complex assembled on DNA and its implications for DNA DSB repair [11].
  • Consistent with this observation, we observed that human cell lines stably expressing dominant-negative constructs of KARP-1 resulted in diminished DNA-PK activity and X-ray hypersensitivity and that a KARP-1 antibody significantly neutralized DNA-PK activity in vitro [12].

Chemical compound and disease context of XRCC5

  • An antisense oligonucleotide targeted to human Ku86 messenger RNA sensitizes M059K malignant glioma cells to ionizing radiation, bleomycin, and etoposide but not DNA cross-linking agents [13].
  • The optimal conditions for the determination of exposure to scrub typhus by the whole blood lymphocyte transformation assay was 7 days culture of 10% blood in RPMI 1640 medium supplemented with 10% human AB-negative serum and L-glutamine with 50-200 micrograms protein/ml of Karp, Kato, or Gilliam strain membrane antigen [14].

Biological context of XRCC5

  • The human XRCC5 DNA repair gene, which complements this mutant, is shown here through genetic and biochemical evidence to be the 80-kilodalton subunit of the Ku protein [10].
  • These data show that the gene defective in xrs cells, XRCC5, which is involved in double-strand break rejoining, is located on human chromosome 2q [15].
  • In contrast, the other mutants defective in NER activities, the XRCC2 and XRCC3 mutants, and the XRCC5 mutant all showed normal unhooking kinetics [16].
  • Assignment of a human DNA double-strand break repair gene (XRCC5) to chromosome 2 [17].
  • Discordancies between some chromosome 2 markers and the radiation resistance phenotype in some of the hybrid cells suggested the location of the X-ray repair cross complementing 5 (XRCC5) gene on the p arm of chromosome 2 [17].

Anatomical context of XRCC5


Associations of XRCC5 with chemical compounds

  • Strikingly, we found that doxazosin induces deregulation of genes implicated in DNA replication and repair, such as GADD45A, XRCC5 and PRKDC [2].
  • Nuclear XRCC5 is normally extractable with non-ionic detergent; it is found in the soluble cytoplasmic fraction after nuclear isolation with Triton X-100 [1].
  • 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 [23].
  • 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 [24].
  • The KARP-1-specific domain encodes interdigitating hexa- and penta-heptad repeats of leucine residues flanked by a very basic region [12].

Physical interactions of XRCC5

  • The atomic structure of a truncated Ku70-Ku80 was determined; however, the subunit-specific carboxy-terminal domain of Ku80-essential for binding to DNA-PKcs-was determined only in isolation, and the C-terminal domain of Ku70 was not resolved in its DNA-bound conformation [25].
  • In addition, our data indicate that the region of Ku80 between amino acids 215 and 276 is necessary for binding to WRN [26].
  • These results indicate that the ATM protein is recruited to the site of DNA damage and it recognizes double strand breaks by itself or through an association with other DNA-binding protein other than DNA-PK and Ku80 proteins [27].

Regulatory relationships of XRCC5

  • Ku70 and Ku80 have been shown to form a heterodimeric complex that can bind tightly to free DNA ends and activate the protein kinase DNA-PKcs [28].
  • KARP-1: a novel leucine zipper protein expressed from the Ku86 autoantigen locus is implicated in the control of DNA-dependent protein kinase activity [12].
  • Although the specific binding of Ku to EBVRE was not demonstrated, dominant negative Ku80 suppressed IL-4 + anti-CD40-driven CD23 expression [29].
  • Our findings are consistent with the hypothesis that somatostatin controls cell cycle progression and DNA repair through a new signalling pathway that involves the regulation of Ku86 level and modulates the Ku70/86 activity in the nucleus [30].

Other interactions of XRCC5

  • Based on the analysis of the structure-function of Ku70 and the crystal structure of Ku70/Ku80 heterodimer, we designed and identified a candidate dominant negative fragment involving an NH(2)-terminal deletion, and designated it as DNKu70 [23].
  • DNA-PK comprises the Ku70/Ku80 heterodimer and the catalytic subunit DNA-PKcs [31].
  • No significant association was found between the repeat length at any of the microsatellites in XRCC1, XRCC3 or XRCC5 and the incidence of late radiotherapy complications [32].
  • Surprisingly, however, even in a p53-null genetic background, the absence of Ku86 proved lethal [22].
  • When specific numbers of repeats were examined, no significant correlation was found between the microsatellite repeat length in XRCC1 and XRCC5 and cancer incidence [32].

Analytical, diagnostic and therapeutic context of XRCC5


  1. Heat-induced aggregation of XRCC5 (Ku80) in nontolerant and thermotolerant cells. Beck, B.D., Dynlacht, J.R. Radiat. Res. (2001) [Pubmed]
  2. Doxazosin induces apoptosis in LNCaP prostate cancer cell line through DNA binding and DNA-dependent protein kinase down-regulation. Arencibia, J.M., Del Rio, M., Bonnin, A., Lopes, R., Lemoine, N.R., López-Barahona, M. Int. J. Oncol. (2005) [Pubmed]
  3. Linkage and association analysis of radiation damage repair genes XRCC3 and XRCC5 with nevus density in adolescent twins. Zhu, G., Duffy, D.L., Turner, D.R., Ewen, K.R., Montgomery, G.W., Martin, N.G. Twin research : the official journal of the International Society for Twin Studies. (2003) [Pubmed]
  4. 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]
  5. 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]
  6. Personality characteristics of incest survivors on the Draw-A-Person Questionnaire. Waldman, T.L., Silber, D.E., Holmstrom, R.W., Karp, S.A. Journal of personality assessment. (1994) [Pubmed]
  7. The relation of reflection-impulsivity to field dependence-independence and internal-external control in children. Massari, D.J. The Journal of genetic psychology ; child behavior, animal behavior, and comparative psychology. (1975) [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. Yeast DNA ligase IV mediates non-homologous DNA end joining. Wilson, T.E., Grawunder, U., Lieber, M.R. Nature (1997) [Pubmed]
  10. Ku80: product of the XRCC5 gene and its role in DNA repair and V(D)J recombination. Taccioli, G.E., Gottlieb, T.M., Blunt, T., Priestley, A., Demengeot, J., Mizuta, R., Lehmann, A.R., Alt, F.W., Jackson, S.P., Jeggo, P.A. Science (1994) [Pubmed]
  11. Three-dimensional structure of the human DNA-PKcs/Ku70/Ku80 complex assembled on DNA and its implications for DNA DSB repair. Spagnolo, L., Rivera-Calzada, A., Pearl, L.H., Llorca, O. Mol. Cell (2006) [Pubmed]
  12. KARP-1: a novel leucine zipper protein expressed from the Ku86 autoantigen locus is implicated in the control of DNA-dependent protein kinase activity. Myung, K., He, D.M., Lee, S.E., Hendrickson, E.A. EMBO J. (1997) [Pubmed]
  13. An antisense oligonucleotide targeted to human Ku86 messenger RNA sensitizes M059K malignant glioma cells to ionizing radiation, bleomycin, and etoposide but not DNA cross-linking agents. Belenkov, A.I., Paiement, J.P., Panasci, L.C., Monia, B.P., Chow, T.Y. Cancer Res. (2002) [Pubmed]
  14. Evaluation of the whole blood lymphocyte transformation assay for scrub typhus exposure: adaptability to field sample collection. Lim, T.S., LaBarre, D.D., Lewis, G.E. Jpn. J. Med. Sci. Biol. (1988) [Pubmed]
  15. Localization of a DNA repair gene (XRCC5) involved in double-strand-break rejoining to human chromosome 2. Jeggo, P.A., Hafezparast, M., Thompson, A.F., Broughton, B.C., Kaur, G.P., Zdzienicka, M.Z., Athwal, R.S. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  16. Defining the roles of nucleotide excision repair and recombination in the repair of DNA interstrand cross-links in mammalian cells. De Silva, I.U., McHugh, P.J., Clingen, P.H., Hartley, J.A. Mol. Cell. Biol. (2000) [Pubmed]
  17. Assignment of a human DNA double-strand break repair gene (XRCC5) to chromosome 2. Chen, D.J., Park, M.S., Campbell, E., Oshimura, M., Liu, P., Zhao, Y., White, B.F., Siciliano, M.J. Genomics (1992) [Pubmed]
  18. Regional assignment of a human DNA repair gene (XRCC5) to 2q35 by X-ray hybrid mapping. Chen, D.J., Marrone, B.L., Nguyen, T., Stackhouse, M., Zhao, Y., Siciliano, M.J. Genomics (1994) [Pubmed]
  19. A YAC contig encompassing the XRCC5 (Ku80) DNA repair gene and complementation of defective cells by YAC protoplast fusion. Blunt, T., Taccioli, G.E., Priestley, A., Hafezparast, M., McMillan, T., Liu, J., Cole, C.C., White, J., Alt, F.W., Jackson, S.P. Genomics (1995) [Pubmed]
  20. Increased expression of human DNA repair genes, XRCC1, XRCC3 and RAD51, in radioresistant human KB carcinoma cell line N10. Yanagisawa, T., Urade, M., Yamamoto, Y., Furuyama, J. Oral Oncol. (1998) [Pubmed]
  21. 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]
  22. The Lethality of Ku86 (XRCC5) Loss-of-Function Mutations in Human Cells is Independent of p53 (TP53). Ghosh, G., Li, G., Myung, K., Hendrickson, E.A. Radiat. Res. (2007) [Pubmed]
  23. 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]
  24. 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]
  25. Structural model of full-length human Ku70-Ku80 heterodimer and its recognition of DNA and DNA-PKcs. Rivera-Calzada, A., Spagnolo, L., Pearl, L.H., Llorca, O. EMBO Rep. (2007) [Pubmed]
  26. 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]
  27. Recruitment of ATM protein to double strand DNA irradiated with ionizing radiation. Suzuki, K., Kodama, S., Watanabe, M. J. Biol. Chem. (1999) [Pubmed]
  28. 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]
  29. Coordinated regulation of the promoter and enhancer regions of human CD23 gene by signal through IL-4R and CD40, and the role of Ku70/80 in the enhancer activity. Imai, M., Mizutani, S., Morio, T. J. Med. Dent. Sci. (2003) [Pubmed]
  30. The expression and the nuclear activity of the caretaker gene ku86 are modulated by somatostatin. Pucci, S., Bonanno, E., Pichiorri, F., Mazzarelli, P., Spagnoli, L.G. European journal of histochemistry : EJH. (2004) [Pubmed]
  31. DNA-dependent protein kinase and XRCC4-DNA ligase IV mobilization in the cell in response to DNA double strand breaks. Drouet, J., Delteil, C., Lefrançois, J., Concannon, P., Salles, B., Calsou, P. J. Biol. Chem. (2005) [Pubmed]
  32. Microsatellite polymorphisms in DNA repair genes XRCC1, XRCC3 and XRCC5 in patients with gynecological tumors: association with late clinical radiosensitivity and cancer incidence. De Ruyck, K., Wilding, C.S., Van Eijkeren, M., Morthier, R., Tawn, E.J., Thierens, H. Radiat. Res. (2005) [Pubmed]
  33. DNA-PK, the DNA-activated protein kinase, is differentially expressed in normal and malignant human tissues. Moll, U., Lau, R., Sypes, M.A., Gupta, M.M., Anderson, C.W. Oncogene (1999) [Pubmed]
  34. Human neutrophils isolated from peripheral blood contain Ku protein but not DNA-dependent protein kinase. Kurosawa, A., Shinohara, K., Watanabe, F., Shimizu-Saito, K., Koiwai, O., Yamamoto, K., Teraoka, H. Int. J. Biochem. Cell Biol. (2003) [Pubmed]
  35. 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]
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