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Ku70

PDB rendering based on 1jeq.
Available structures
1jeq, 1jey
Identifiers
Symbols XRCC6; CTC75; CTCBF; G22P1; KU70; ML8; TLAA
External IDs OMIM152690 MGI95606 HomoloGene37483 GeneCards: XRCC6 Gene
Orthologs
Species Human Mouse
Entrez 2547 14375
Ensembl n/a ENSMUSG00000022471
UniProt n/a Q3UJL8
RefSeq (mRNA) NM_001469 NM_010247
RefSeq (protein) NP_001460 NP_034377
Location (UCSC) n/a Chr 15:
81.84 - 81.87 Mb
PubMed search [1] [2]

Ku70 is a protein which in humans is encoded by the XRCC6 gene.[1] Together, Ku70 and Ku80 make up the Ku heterodimer, which binds to DNA double-strand break ends and is required for the non-homologous end joining (NHEJ) pathway of DNA repair. It is also required for V(D)J recombination, which utilizes the NHEJ pathway to promote antigen diversity in the mammalian immune system.

In additon to its role in NHEJ, Ku is also required for telomere length maintenance and subtelomeric gene silencing.[2]

Ku was originally identified when patients with systemic lupus erythematosus were found to have high levels of autoantibodies to the protein.[1]

Historically, Ku70 has been referred to by several names including:

  • Lupus Ku autoantigen protein p70
  • ATP-dependent DNA helicase 2 subunit 1
  • X-ray repair complementing defective repair in Chinese hamster cells 6
  • X-ray repair cross-complementing 6 (XRCC6)

Interactions

Ku70 has been shown to interact with GCN5L2,[3] PTTG1,[4] HOXC4,[5] CHEK1,[6] Werner syndrome ATP-dependent helicase,[7][8] RPA2,[9] CBX5,[10] CREB binding protein,[3] Neutrophil cytosolic factor 4,[11] MRE11A,[12] NCOA6,[13][14] Ku80,[15][3][16][17][18] TERF2,[18] VAV1,[19] Telomerase reverse transcriptase[20] and PCNA.[21][22]

References

  1. ^ a b "Entrez Gene: XRCC6 X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2547.  
  2. ^ Boulton SJ, Jackson SP (March 1998). "Components of the Ku-dependent non-homologous end-joining pathway are involved in telomeric length maintenance and telomeric silencing". EMBO J. 17 (6): 1819–28. doi:10.1093/emboj/17.6.1819. PMID 9501103.  
  3. ^ a b c Barlev, N A; Poltoratsky V, Owen-Hughes T, Ying C, Liu L, Workman J L, Berger S L (Mar. 1998). "Repression of GCN5 histone acetyltransferase activity via bromodomain-mediated binding and phosphorylation by the Ku-DNA-dependent protein kinase complex". Mol. Cell. Biol. (UNITED STATES) 18 (3): 1349–58. ISSN 0270-7306. PMID 9488450.  
  4. ^ Romero, F; Multon M C, Ramos-Morales F, Domínguez A, Bernal J A, Pintor-Toro J A, Tortolero M (Mar. 2001). "Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase". Nucleic Acids Res. (England) 29 (6): 1300–7. PMID 11238996.  
  5. ^ Schild-Poulter, C; Pope L, Giffin W, Kochan J C, Ngsee J K, Traykova-Andonova M, Haché R J (May. 2001). "The binding of Ku antigen to homeodomain proteins promotes their phosphorylation by DNA-dependent protein kinase". J. Biol. Chem. (United States) 276 (20): 16848–56. doi:10.1074/jbc.M100768200. ISSN 0021-9258. PMID 11279128.  
  6. ^ Goudelock, Dawn Marie; Jiang Kecheng, Pereira Elizabeth, Russell Beatriz, Sanchez Yolanda (Aug. 2003). "Regulatory interactions between the checkpoint kinase Chk1 and the proteins of the DNA-dependent protein kinase complex". J. Biol. Chem. (United States) 278 (32): 29940–7. doi:10.1074/jbc.M301765200. ISSN 0021-9258. PMID 12756247.  
  7. ^ Karmakar, Parimal; Snowden Carey M, Ramsden Dale A, Bohr Vilhelm A (Aug. 2002). "Ku heterodimer binds to both ends of the Werner protein and functional interaction occurs at the Werner N-terminus". Nucleic Acids Res. (England) 30 (16): 3583–91. PMID 12177300.  
  8. ^ Li, B; Comai L (Sep. 2000). "Functional interaction between Ku and the werner syndrome protein in DNA end processing". J. Biol. Chem. (UNITED STATES) 275 (37): 28349–52. doi:10.1074/jbc.C000289200. ISSN 0021-9258. PMID 10880505.  
  9. ^ Shao, R G; Cao C X, Zhang H, Kohn K W, Wold M S, Pommier Y (Mar. 1999). "Replication-mediated DNA damage by camptothecin induces phosphorylation of RPA by DNA-dependent protein kinase and dissociates RPA:DNA-PK complexes". EMBO J. (ENGLAND) 18 (5): 1397–406. doi:10.1093/emboj/18.5.1397. ISSN 0261-4189. PMID 10064605.  
  10. ^ Song, K; Jung Y, Jung D, Lee I (Mar. 2001). "Human Ku70 interacts with heterochromatin protein 1alpha". J. Biol. Chem. (United States) 276 (11): 8321–7. doi:10.1074/jbc.M008779200. ISSN 0021-9258. PMID 11112778.  
  11. ^ Grandvaux, N; Grizot S, Vignais P V, Dagher M C (Feb. 1999). "The Ku70 autoantigen interacts with p40phox in B lymphocytes". J. Cell. Sci. (ENGLAND) 112 ( Pt 4): 503–13. ISSN 0021-9533. PMID 9914162.  
  12. ^ Goedecke, W; Eijpe M, Offenberg H H, van Aalderen M, Heyting C (Oct. 1999). "Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis". Nat. Genet. (UNITED STATES) 23 (2): 194–8. doi:10.1038/13821. ISSN 1061-4036. PMID 10508500.  
  13. ^ Ko, L; Cardona G R, Chin W W (May. 2000). "Thyroid hormone receptor-binding protein, an LXXLL motif-containing protein, functions as a general coactivator". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (11): 6212–7. ISSN 0027-8424. PMID 10823961.  
  14. ^ Ko, Lan; Chin William W (Mar. 2003). "Nuclear receptor coactivator thyroid hormone receptor-binding protein (TRBP) interacts with and stimulates its associated DNA-dependent protein kinase". J. Biol. Chem. (United States) 278 (13): 11471–9. doi:10.1074/jbc.M209723200. ISSN 0021-9258. PMID 12519782.  
  15. ^ Gell, D; Jackson S P (Sep. 1999). "Mapping of protein-protein interactions within the DNA-dependent protein kinase complex". Nucleic Acids Res. (ENGLAND) 27 (17): 3494–502. PMID 10446239.  
  16. ^ Yang, C R; Yeh S, Leskov K, Odegaard E, Hsu H L, Chang C, Kinsella T J, Chen D J, Boothman D A (May. 1999). "Isolation of Ku70-binding proteins (KUBs)". Nucleic Acids Res. (ENGLAND) 27 (10): 2165–74. ISSN 0305-1048. PMID 10219089.  
  17. ^ Singleton, B K; Torres-Arzayus M I, Rottinghaus S T, Taccioli G E, Jeggo P A (May. 1999). "The C terminus of Ku80 activates the DNA-dependent protein kinase catalytic subunit". Mol. Cell. Biol. (UNITED STATES) 19 (5): 3267–77. ISSN 0270-7306. PMID 10207052.  
  18. ^ a b Song, K; Jung D, Jung Y, Lee S G, Lee I (Sep. 2000). "Interaction of human Ku70 with TRF2". FEBS Lett. (NETHERLANDS) 481 (1): 81–5. ISSN 0014-5793. PMID 10984620.  
  19. ^ Romero, F; Dargemont C, Pozo F, Reeves W H, Camonis J, Gisselbrecht S, Fischer S (Jan. 1996). "p95vav associates with the nuclear protein Ku-70". Mol. Cell. Biol. (UNITED STATES) 16 (1): 37–44. ISSN 0270-7306. PMID 8524317.  
  20. ^ Chai, Weihang; Ford Lance P, Lenertz Lisa, Wright Woodring E, Shay Jerry W (Dec. 2002). "Human Ku70/80 associates physically with telomerase through interaction with hTERT". J. Biol. Chem. (United States) 277 (49): 47242–7. doi:10.1074/jbc.M208542200. ISSN 0021-9258. PMID 12377759.  
  21. ^ Ohta, Satoshi; Shiomi Yasushi, Sugimoto Katsunori, Obuse Chikashi, Tsurimoto Toshiki (Oct. 2002). "A proteomics approach to identify proliferating cell nuclear antigen (PCNA)-binding proteins in human cell lysates. Identification of the human CHL12/RFCs2-5 complex as a novel PCNA-binding protein". J. Biol. Chem. (United States) 277 (43): 40362–7. doi:10.1074/jbc.M206194200. ISSN 0021-9258. PMID 12171929.  
  22. ^ Balajee, A S; Geard C R (Mar. 2001). "Chromatin-bound PCNA complex formation triggered by DNA damage occurs independent of the ATM gene product in human cells". Nucleic Acids Res. (England) 29 (6): 1341–51. PMID 11239001.  

Further reading

  • Smider V, Chu G (1997). "The end-joining reaction in V(D)J recombination.". Semin. Immunol. 9 (3): 189–97. doi:10.1006/smim.1997.0070. PMID 9200330.  
  • Featherstone C, Jackson SP (1999). "Ku, a DNA repair protein with multiple cellular functions?". Mutat. Res. 434 (1): 3–15. PMID 10377944.  
  • Koike M (2003). "Dimerization, translocation and localization of Ku70 and Ku80 proteins.". J. Radiat. Res. 43 (3): 223–36. PMID 12518983.  
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