Ku80
Ku80 is a protein that, in humans, is encoded by the XRCC5 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 addition to its role in NHEJ, Ku is 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]
Ku80 has been referred to by several names including:
- Lupus Ku autoantigen protein p80
- ATP-dependent DNA helicase 2 subunit 2
- X-ray repair complementing defective repair in Chinese hamster cells 5
- X-ray repair cross-complementing 5 (XRCC5)
Clinical significance
A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity.[1]
Interactions
Ku80 has been shown to interact with NCOA6,[3][4] GCN5L2,[5] Ku70,[5][6][7][8][9] Werner syndrome ATP-dependent helicase,[10][11] Tyrosine kinase 2,[12] DNA-PKcs,[6][13][14] TERF2IP,[15] Telomerase reverse transcriptase,[16] POU2F1[14][17] and PCNA.[14][18][19]
References
- ↑ 1.0 1.1 1.2 "Entrez Gene: XRCC6 X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa)".
- ↑ 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.
- ↑ 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. doi:10.1073/pnas.97.11.6212. ISSN 0027-8424. PMC 18584. PMID 10823961.
- ↑ Ko, Lan; Chin William W (March 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.
- ↑ 5.0 5.1 Barlev, N A; Poltoratsky V, Owen-Hughes T, Ying C, Liu L, Workman J L, Berger S L (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. (United States) 18 (3): 1349–58. ISSN 0270-7306. PMC 108848. PMID 9488450.
- ↑ 6.0 6.1 Gell, D; Jackson S P (September 1999). "Mapping of protein-protein interactions within the DNA-dependent protein kinase complex". Nucleic Acids Res. (ENGLAND) 27 (17): 3494–502. doi:10.1093/nar/27.17.3494. PMC 148593. PMID 10446239.
- ↑ 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. doi:10.1093/nar/27.10.2165. ISSN 0305-1048. PMC 148436. PMID 10219089.
- ↑ 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. PMC 84121. PMID 10207052.
- ↑ Song, K; Jung D, Jung Y, Lee S G, Lee I (September 2000). "Interaction of human Ku70 with TRF2". FEBS Lett. (NETHERLANDS) 481 (1): 81–5. doi:10.1016/S0014-5793(00)01958-X. ISSN 0014-5793. PMID 10984620.
- ↑ Karmakar, Parimal; Snowden Carey M, Ramsden Dale A, Bohr Vilhelm A (August 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. doi:10.1093/nar/gkf482. PMC 134248. PMID 12177300.
- ↑ Li, B; Comai L (September 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.
- ↑ Adam, L; Bandyopadhyay D, Kumar R (January 2000). "Interferon-alpha signaling promotes nucleus-to-cytoplasmic redistribution of p95Vav, and formation of a multisubunit complex involving Vav, Ku80, and Tyk2". Biochem. Biophys. Res. Commun. (United States) 267 (3): 692–6. doi:10.1006/bbrc.1999.1978. ISSN 0006-291X. PMID 10673353.
- ↑ Jin, S; Kharbanda S, Mayer B, Kufe D, Weaver D T (October 1997). "Binding of Ku and c-Abl at the kinase homology region of DNA-dependent protein kinase catalytic subunit". J. Biol. Chem. (United States) 272 (40): 24763–6. doi:10.1074/jbc.272.40.24763. ISSN 0021-9258. PMID 9312071.
- ↑ 14.0 14.1 14.2 Matheos, Diamanto; Ruiz Marcia T, Price Gerald B, Zannis-Hadjopoulos Maria (October 2002). "Ku antigen, an origin-specific binding protein that associates with replication proteins, is required for mammalian DNA replication". Biochim. Biophys. Acta (Netherlands) 1578 (1-3): 59–72. doi:10.1016/S0167-4781(02)00497-9. ISSN 0006-3002. PMID 12393188.
- ↑ O'Connor, Matthew S; Safari Amin, Liu Dan, Qin Jun, Songyang Zhou (July 2004). "The human Rap1 protein complex and modulation of telomere length". J. Biol. Chem. (United States) 279 (27): 28585–91. doi:10.1074/jbc.M312913200. ISSN 0021-9258. PMID 15100233.
- ↑ Chai, Weihang; Ford Lance P, Lenertz Lisa, Wright Woodring E, Shay Jerry W (December 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.
- ↑ 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.
- ↑ Ohta, Satoshi; Shiomi Yasushi, Sugimoto Katsunori, Obuse Chikashi, Tsurimoto Toshiki (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. (United States) 277 (43): 40362–7. doi:10.1074/jbc.M206194200. ISSN 0021-9258. PMID 12171929.
- ↑ Balajee, A S; Geard C R (March 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. doi:10.1093/nar/29.6.1341. PMC 29758. PMID 11239001.
Further reading
- Koike M (2003). "Dimerization, translocation and localization of Ku70 and Ku80 proteins.". J. Radiat. Res. 43 (3): 223–36. doi:10.1269/jrr.43.223. PMID 12518983.
- Chen DJ, Park MS, Campbell E, et al. (1992). "Assignment of a human DNA double-strand break repair gene (XRCC5) to chromosome 2.". Genomics 13 (4): 1088–94. doi:10.1016/0888-7543(92)90023-L. PMID 1505945.
- Wedrychowski A, Henzel W, Huston L, et al. (1992). "Identification of proteins binding to interferon-inducible transcriptional enhancers in hematopoietic cells.". J. Biol. Chem. 267 (7): 4533–40. PMID 1537839.
- Jeggo PA, Hafezparast M, Thompson AF, et al. (1992). "Localization of a DNA repair gene (XRCC5) involved in double-strand-break rejoining to human chromosome 2.". Proc. Natl. Acad. Sci. U.S.A. 89 (14): 6423–7. doi:10.1073/pnas.89.14.6423. PMC 49513. PMID 1631138.
- Knuth MW, Gunderson SI, Thompson NE, et al. (1990). "Purification and characterization of proximal sequence element-binding protein 1, a transcription activating protein related to Ku and TREF that binds the proximal sequence element of the human U1 promoter.". J. Biol. Chem. 265 (29): 17911–20. PMID 2211668.
- Stuiver MH, Coenjaerts FE, van der Vliet PC (1990). "The autoantigen Ku is indistinguishable from NF IV, a protein forming multimeric protein-DNA complexes.". J. Exp. Med. 172 (4): 1049–54. doi:10.1084/jem.172.4.1049. PMC 2188621. PMID 2212941.
- Mimori T, Ohosone Y, Hama N, et al. (1990). "Isolation and characterization of cDNA encoding the 80-kDa subunit protein of the human autoantigen Ku (p70/p80) recognized by autoantibodies from patients with scleroderma-polymyositis overlap syndrome.". Proc. Natl. Acad. Sci. U.S.A. 87 (5): 1777–81. doi:10.1073/pnas.87.5.1777. PMC 53566. PMID 2308937.
- Yaneva M, Wen J, Ayala A, Cook R (1989). "cDNA-derived amino acid sequence of the 86-kDa subunit of the Ku antigen.". J. Biol. Chem. 264 (23): 13407–11. PMID 2760028.
- Genersch E, Eckerskorn C, Lottspeich F, et al. (1995). "Purification of the sequence-specific transcription factor CTCBF, involved in the control of human collagen IV genes: subunits with homology to Ku antigen.". EMBO J. 14 (4): 791–800. PMC 398145. PMID 7882982.
- Tuteja N, Tuteja R, Ochem A, et al. (1994). "Human DNA helicase II: a novel DNA unwinding enzyme identified as the Ku autoantigen.". EMBO J. 13 (20): 4991–5001. PMC 395441. PMID 7957065.
- Le Romancer M, Reyl-Desmars F, Cherifi Y, et al. (1994). "The 86-kDa subunit of autoantigen Ku is a somatostatin receptor regulating protein phosphatase-2A activity.". J. Biol. Chem. 269 (26): 17464–8. PMID 8021251.
- Cao QP, Pitt S, Leszyk J, Baril EF (1994). "DNA-dependent ATPase from HeLa cells is related to human Ku autoantigen.". Biochemistry 33 (28): 8548–57. doi:10.1021/bi00194a021. PMID 8031790.
- Taccioli GE, Gottlieb TM, Blunt T, et al. (1994). "Ku80: product of the XRCC5 gene and its role in DNA repair and V(D)J recombination.". Science 265 (5177): 1442–5. doi:10.1126/science.8073286. PMID 8073286.
- Chen DJ, Marrone BL, Nguyen T, et al. (1994). "Regional assignment of a human DNA repair gene (XRCC5) to 2q35 by X-ray hybrid mapping.". Genomics 21 (2): 423–7. doi:10.1006/geno.1994.1287. PMID 8088837.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Kaczmarski W, Khan SA (1993). "Lupus autoantigen Ku protein binds HIV-1 TAR RNA in vitro.". Biochem. Biophys. Res. Commun. 196 (2): 935–42. doi:10.1006/bbrc.1993.2339. PMID 8240370.
- Blunt T, Taccioli GE, Priestley A, et al. (1996). "A YAC contig encompassing the XRCC5 (Ku80) DNA repair gene and complementation of defective cells by YAC protoplast fusion.". Genomics 30 (2): 320–8. doi:10.1006/geno.1995.9871. PMID 8586433.
- Warriar N, Pagé N, Govindan MV (1996). "Expression of human glucocorticoid receptor gene and interaction of nuclear proteins with the transcriptional control element.". J. Biol. Chem. 271 (31): 18662–71. doi:10.1074/jbc.271.31.18662. PMID 8702520.
- Myung K, He DM, Lee SE, Hendrickson EA (1997). "KARP-1: a novel leucine zipper protein expressed from the Ku86 autoantigen locus is implicated in the control of DNA-dependent protein kinase activity.". EMBO J. 16 (11): 3172–84. doi:10.1093/emboj/16.11.3172. PMC 1169935. PMID 9214634.
- Jin S, Kharbanda S, Mayer B, et al. (1997). "Binding of Ku and c-Abl at the kinase homology region of DNA-dependent protein kinase catalytic subunit.". J. Biol. Chem. 272 (40): 24763–6. doi:10.1074/jbc.272.40.24763. PMID 9312071.
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