Ku70

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X-ray repair complementing defective repair in Chinese hamster cells 6
Protein XRCC6 PDB 1jeq.png
PDB rendering based on 1jeq.
Available structures
PDB Ortholog search: PDBe, RCSB
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 ENSG00000196419 ENSMUSG00000022471
UniProt P12956 P23475
RefSeq (mRNA) NM_001288976 NM_010247
RefSeq (protein) NP_001275905 NP_034377
Location (UCSC) Chr 22:
42.02 – 42.06 Mb
Chr 15:
81.99 – 82.04 Mb
PubMed search [1] [2]

Ku70 is a protein that, in humans, is encoded by the XRCC6 gene.[1][2]

Function[edit]

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 addition to its role in NHEJ, Ku is also required for telomere length maintenance and subtelomeric gene silencing.[3]

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

Aging[edit]

Mouse embryonic stem cells with homozygous Ku70 mutations, that is Ku70(-/-) cells, have markedly increased sensitivity to ionizing radiation compared to heterozygous Ku70(+/-) or wild-type Ku70(+/+) embryonic stem cells.[4] Mutant mice deficient in Ku70 exhibit early aging.[5] Using several specific criteria of aging, the mutant mice were found to display the same aging signs as control mice, but at a considerably earlier chronological age. These results suggest that reduced ability to repair DNA double-strand breaks causes early aging, and that the wild-type Ku70 gene plays an important role in longevity assurance.[6] (Also see DNA damage theory of aging.)

Nomenclature[edit]

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[edit]

Ku70 has been shown to interact with:


References[edit]

  1. ^ a b "Entrez Gene: XRCC6 X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa)". 
  2. ^ Pace, P; Mosedale, G; Hodskinson, M. R.; Rosado, I. V.; Sivasubramaniam, M; Patel, K. J. (2010). "Ku70 corrupts DNA repair in the absence of the Fanconi anemia pathway". Science 329 (5988): 219–23. doi:10.1126/science.1192277. PMID 20538911. 
  3. ^ 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. PMC 1170529. PMID 9501103. 
  4. ^ Gu Y, Jin S, Gao Y, Weaver DT, Alt FW (1997). "Ku70-deficient embryonic stem cells have increased ionizing radiosensitivity, defective DNA end-binding activity, and inability to support V(D)J recombination". Proc. Natl. Acad. Sci. U.S.A. 94 (15): 8076–81. PMC 21559. PMID 9223317. 
  5. ^ Li H, Vogel H, Holcomb VB, Gu Y, Hasty P (2007). "Deletion of Ku70, Ku80, or both causes early aging without substantially increased cancer". Mol. Cell. Biol. 27 (23): 8205–14. doi:10.1128/MCB.00785-07. PMC 2169178. PMID 17875923. 
  6. ^ Bernstein H, Payne CM, Bernstein C, Garewal H, Dvorak K (2008). Cancer and aging as consequences of un-repaired DNA damage. In: New Research on DNA Damages (Editors: Honoka Kimura and Aoi Suzuki) Nova Science Publishers, Inc., New York, Chapter 1, pp. 1-47. open access, but read only https://www.novapublishers.com/catalog/product_info.php?products_id=43247 ISBN 978-1604565812
  7. ^ Song K, Jung Y, Jung D, Lee I (March 2001). "Human Ku70 interacts with heterochromatin protein 1alpha". J. Biol. Chem. 276 (11): 8321–7. doi:10.1074/jbc.M008779200. PMID 11112778. 
  8. ^ Goudelock DM, Jiang K, Pereira E, Russell B, Sanchez Y (August 2003). "Regulatory interactions between the checkpoint kinase Chk1 and the proteins of the DNA-dependent protein kinase complex". J. Biol. Chem. 278 (32): 29940–7. doi:10.1074/jbc.M301765200. PMID 12756247. 
  9. ^ a b c Barlev NA, Poltoratsky V, Owen-Hughes T, Ying C, Liu L, Workman JL et al. (March 1998). "Repression of GCN5 histone acetyltransferase activity via bromodomain-mediated binding and phosphorylation by the Ku-DNA-dependent protein kinase complex". Mol. Cell. Biol. 18 (3): 1349–58. PMC 108848. PMID 9488450. 
  10. ^ Schild-Poulter C, Pope L, Giffin W, Kochan JC, Ngsee JK, Traykova-Andonova M et al. (May 2001). "The binding of Ku antigen to homeodomain proteins promotes their phosphorylation by DNA-dependent protein kinase". J. Biol. Chem. 276 (20): 16848–56. doi:10.1074/jbc.M100768200. PMID 11279128. 
  11. ^ Gell D, Jackson SP (September 1999). "Mapping of protein-protein interactions within the DNA-dependent protein kinase complex". Nucleic Acids Res. 27 (17): 3494–502. doi:10.1093/nar/27.17.3494. PMC 148593. PMID 10446239. 
  12. ^ Yang CR, Yeh S, Leskov K, Odegaard E, Hsu HL, Chang C et al. (May 1999). "Isolation of Ku70-binding proteins (KUBs)". Nucleic Acids Res. 27 (10): 2165–74. doi:10.1093/nar/27.10.2165. PMC 148436. PMID 10219089. 
  13. ^ Singleton BK, Torres-Arzayus MI, Rottinghaus ST, Taccioli GE, Jeggo PA (May 1999). "The C terminus of Ku80 activates the DNA-dependent protein kinase catalytic subunit". Mol. Cell. Biol. 19 (5): 3267–77. PMC 84121. PMID 10207052. 
  14. ^ a b Song K, Jung D, Jung Y, Lee SG, Lee I (September 2000). "Interaction of human Ku70 with TRF2". FEBS Lett. 481 (1): 81–5. doi:10.1016/S0014-5793(00)01958-X. PMID 10984620. 
  15. ^ Goedecke W, Eijpe M, Offenberg HH, van Aalderen M, Heyting C (October 1999). "Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis". Nat. Genet. 23 (2): 194–8. doi:10.1038/13821. PMID 10508516. 
  16. ^ Ko L, Cardona GR, Chin WW (May 2000). "Thyroid hormone receptor-binding protein, an LXXLL motif-containing protein, functions as a general coactivator". Proc. Natl. Acad. Sci. U.S.A. 97 (11): 6212–7. doi:10.1073/pnas.97.11.6212. PMC 18584. PMID 10823961. 
  17. ^ Ko L, Chin WW (March 2003). "Nuclear receptor coactivator thyroid hormone receptor-binding protein (TRBP) interacts with and stimulates its associated DNA-dependent protein kinase". J. Biol. Chem. 278 (13): 11471–9. doi:10.1074/jbc.M209723200. PMID 12519782. 
  18. ^ Grandvaux N, Grizot S, Vignais PV, Dagher MC (February 1999). "The Ku70 autoantigen interacts with p40phox in B lymphocytes". J. Cell. Sci. 112 (4): 503–13. PMID 9914162. 
  19. ^ Ohta S, Shiomi Y, Sugimoto K, Obuse C, Tsurimoto T (October 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. 277 (43): 40362–7. doi:10.1074/jbc.M206194200. PMID 12171929. 
  20. ^ Balajee AS, Geard CR (March 2001). "Chromatin-bound PCNA complex formation triggered by DNA damage occurs independent of the ATM gene product in human cells". Nucleic Acids Res. 29 (6): 1341–51. doi:10.1093/nar/29.6.1341. PMC 29758. PMID 11239001. 
  21. ^ Romero F, Multon MC, Ramos-Morales F, Domínguez A, Bernal JA, Pintor-Toro JA et al. (March 2001). "Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase". Nucleic Acids Res. 29 (6): 1300–7. doi:10.1093/nar/29.6.1300. PMC 29753. PMID 11238996. 
  22. ^ Shao RG, Cao CX, Zhang H, Kohn KW, Wold MS, Pommier Y (March 1999). "Replication-mediated DNA damage by camptothecin induces phosphorylation of RPA by DNA-dependent protein kinase and dissociates RPA:DNA-PK complexes". EMBO J. 18 (5): 1397–406. doi:10.1093/emboj/18.5.1397. PMC 1171229. PMID 10064605. 
  23. ^ Chai W, Ford LP, Lenertz L, Wright WE, Shay JW (December 2002). "Human Ku70/80 associates physically with telomerase through interaction with hTERT". J. Biol. Chem. 277 (49): 47242–7. doi:10.1074/jbc.M208542200. PMID 12377759. 
  24. ^ Romero F, Dargemont C, Pozo F, Reeves WH, Camonis J, Gisselbrecht S et al. (January 1996). "p95vav associates with the nuclear protein Ku-70". Mol. Cell. Biol. 16 (1): 37–44. PMC 230976. PMID 8524317. 
  25. ^ Karmakar P, Snowden CM, Ramsden DA, Bohr VA (August 2002). "Ku heterodimer binds to both ends of the Werner protein and functional interaction occurs at the Werner N-terminus". Nucleic Acids Res. 30 (16): 3583–91. doi:10.1093/nar/gkf482. PMC 134248. PMID 12177300. 
  26. ^ Li B, Comai L (September 2000). "Functional interaction between Ku and the werner syndrome protein in DNA end processing". J. Biol. Chem. 275 (37): 28349–52. doi:10.1074/jbc.C000289200. PMID 10880505. 

Further reading[edit]