Protein found in humans
Ku70 is a protein that, in humans, is encoded by the XRCC6 gene .[ 5] [ 6]
Function
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.[ 7]
Ku was originally identified when patients with systemic lupus erythematosus were found to have high levels of autoantibodies to the protein.[ 5]
Aging
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.[ 8] [ 9] [ 10] DNA damage theory of aging .)
Clinical
A mutation in this gene has been described in a set of 24 families with autism .[ 11]
Nomenclature
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:
CBX5 ,[ 12] CHEK1 ,[ 13] CREBBP ,[ 14] GCN5L2 ,[ 14] HOXC4 ,[ 15] Ku80 ,[ 14] [ 16] [ 17] [ 18] [ 19] MRE11A ,[ 20] NCOA6 ,[ 21] [ 22] NCF4 ,[ 23] PCNA ,[ 24] [ 25] PTTG1 ,[ 26] RPA2 ,[ 27] TERF2 ,[ 19] TERT [ 28] VAV1 ,[ 29] WRN .[ 30] [ 31]
References
^ a b c GRCh38: Ensembl release 89: ENSG00000196419 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022471 – Ensembl , May 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ a b "Entrez Gene: XRCC6 X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa)" .^ Pace P, Mosedale G, Hodskinson MR, Rosado IV, Sivasubramaniam M, Patel KJ (Jul 2010). "Ku70 corrupts DNA repair in the absence of the Fanconi anemia pathway". Science . 329 (5988): 219– 23. Bibcode :2010Sci...329..219P . doi :10.1126/science.1192277 . PMID 20538911 . S2CID 206527645 . ^ Boulton SJ, Jackson SP (Mar 1998). "Components of the Ku-dependent non-homologous end-joining pathway are involved in telomeric length maintenance and telomeric silencing" . The EMBO Journal . 17 (6): 1819– 28. doi :10.1093/emboj/17.6.1819 . PMC 1170529 PMID 9501103 . ^ Gu Y, Jin S, Gao Y, Weaver DT, Alt FW (Jul 1997). "Ku70-deficient embryonic stem cells have increased ionizing radiosensitivity, defective DNA end-binding activity, and inability to support V(D)J recombination" . Proceedings of the National Academy of Sciences of the United States of America . 94 (15): 8076– 81. Bibcode :1997PNAS...94.8076G . doi :10.1073/pnas.94.15.8076 PMC 21559 PMID 9223317 . ^ Li H, Vogel H, Holcomb VB, Gu Y, Hasty P (Dec 2007). "Deletion of Ku70, Ku80, or both causes early aging without substantially increased cancer" . Molecular and Cellular Biology . 27 (23): 8205– 14. doi :10.1128/MCB.00785-07 . PMC 2169178 PMID 17875923 . ^ 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 Archived 2014-10-25 at the Wayback Machine ISBN 978-1604565812
^ Sjaarda CP, Wood S, McNaughton AJ, Taylor S, Hudson ML, Liu X, Guerin A, Ayub M (December 2019). "Exome sequencing identifies de novo splicing variant in XRCC6 in sporadic case of autism". Journal of Human Genetics . 65 (3): 287– 296. doi :10.1038/s10038-019-0707-0 . PMID 31827253 . S2CID 209312195 . ^ Song K, Jung Y, Jung D, Lee I (Mar 2001). "Human Ku70 interacts with heterochromatin protein 1alpha" . The Journal of Biological Chemistry . 276 (11): 8321– 7. doi :10.1074/jbc.M008779200 PMID 11112778 . ^ Goudelock DM, Jiang K, Pereira E, Russell B, Sanchez Y (Aug 2003). "Regulatory interactions between the checkpoint kinase Chk1 and the proteins of the DNA-dependent protein kinase complex" . The Journal of Biological Chemistry . 278 (32): 29940– 7. doi :10.1074/jbc.M301765200 PMID 12756247 . ^ a b c Barlev NA, Poltoratsky V, Owen-Hughes T, Ying C, Liu L, Workman JL, Berger SL (Mar 1998). "Repression of GCN5 histone acetyltransferase activity via bromodomain-mediated binding and phosphorylation by the Ku-DNA-dependent protein kinase complex" . Molecular and Cellular Biology . 18 (3): 1349– 58. doi :10.1128/mcb.18.3.1349 . PMC 108848 PMID 9488450 . ^ Schild-Poulter C, Pope L, Giffin W, Kochan JC, Ngsee JK, Traykova-Andonova M, Haché RJ (May 2001). "The binding of Ku antigen to homeodomain proteins promotes their phosphorylation by DNA-dependent protein kinase" . The Journal of Biological Chemistry . 276 (20): 16848– 56. doi :10.1074/jbc.M100768200 PMID 11279128 . ^ Gell D, Jackson SP (Sep 1999). "Mapping of protein-protein interactions within the DNA-dependent protein kinase complex" . Nucleic Acids Research . 27 (17): 3494– 502. doi :10.1093/nar/27.17.3494 . PMC 148593 PMID 10446239 . ^ Yang CR, Yeh S, Leskov K, Odegaard E, Hsu HL, Chang C, Kinsella TJ, Chen DJ, Boothman DA (May 1999). "Isolation of Ku70-binding proteins (KUBs)" . Nucleic Acids Research . 27 (10): 2165– 74. doi :10.1093/nar/27.10.2165 . PMC 148436 PMID 10219089 . ^ 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" (PDF) . Molecular and Cellular Biology . 19 (5): 3267– 77. doi :10.1128/mcb.19.5.3267 . PMC 84121 PMID 10207052 . ^ a b Song K, Jung D, Jung Y, Lee SG, Lee I (Sep 2000). "Interaction of human Ku70 with TRF2" . FEBS Letters . 481 (1): 81– 5. doi :10.1016/S0014-5793(00)01958-X PMID 10984620 . ^ Goedecke W, Eijpe M, Offenberg HH, van Aalderen M, Heyting C (Oct 1999). "Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis". Nature Genetics . 23 (2): 194– 8. doi :10.1038/13821 . PMID 10508516 . S2CID 13443404 . ^ Ko L, Cardona GR, Chin WW (May 2000). "Thyroid hormone receptor-binding protein, an LXXLL motif-containing protein, functions as a general coactivator" . Proceedings of the National Academy of Sciences of the United States of America . 97 (11): 6212– 7. Bibcode :2000PNAS...97.6212K . doi :10.1073/pnas.97.11.6212 PMC 18584 PMID 10823961 . ^ Ko L, Chin WW (Mar 2003). "Nuclear receptor coactivator thyroid hormone receptor-binding protein (TRBP) interacts with and stimulates its associated DNA-dependent protein kinase" . The Journal of Biological Chemistry . 278 (13): 11471– 9. doi :10.1074/jbc.M209723200 PMID 12519782 . ^ Grandvaux N, Grizot S, Vignais PV, Dagher MC (Feb 1999). "The Ku70 autoantigen interacts with p40phox in B lymphocytes". Journal of Cell Science . 112 (4): 503– 13. doi :10.1242/jcs.112.4.503 . PMID 9914162 . ^ Ohta S, Shiomi Y, Sugimoto K, Obuse C, Tsurimoto T (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" . The Journal of Biological Chemistry . 277 (43): 40362– 7. doi :10.1074/jbc.M206194200 PMID 12171929 . ^ Balajee AS, Geard CR (Mar 2001). "Chromatin-bound PCNA complex formation triggered by DNA damage occurs independent of the ATM gene product in human cells" . Nucleic Acids Research . 29 (6): 1341– 51. doi :10.1093/nar/29.6.1341 . PMC 29758 PMID 11239001 . ^ Romero F, Multon MC, Ramos-Morales F, Domínguez A, Bernal JA, Pintor-Toro JA, Tortolero M (Mar 2001). "Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase" . Nucleic Acids Research . 29 (6): 1300– 7. doi :10.1093/nar/29.6.1300 . PMC 29753 PMID 11238996 . ^ Shao RG, Cao CX, Zhang H, Kohn KW, Wold MS, 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" . The EMBO Journal . 18 (5): 1397– 406. doi :10.1093/emboj/18.5.1397 . PMC 1171229 PMID 10064605 . ^ Chai W, Ford LP, Lenertz L, Wright WE, Shay JW (Dec 2002). "Human Ku70/80 associates physically with telomerase through interaction with hTERT" . The Journal of Biological Chemistry . 277 (49): 47242– 7. doi :10.1074/jbc.M208542200 PMID 12377759 . ^ Romero F, Dargemont C, Pozo F, Reeves WH, Camonis J, Gisselbrecht S, Fischer S (Jan 1996). "p95vav associates with the nuclear protein Ku-70" . Molecular and Cellular Biology . 16 (1): 37– 44. doi :10.1128/mcb.16.1.37 . PMC 230976 PMID 8524317 . ^ Karmakar P, Snowden CM, Ramsden DA, Bohr VA (Aug 2002). "Ku heterodimer binds to both ends of the Werner protein and functional interaction occurs at the Werner N-terminus" . Nucleic Acids Research . 30 (16): 3583– 91. doi :10.1093/nar/gkf482 . PMC 134248 PMID 12177300 . ^ Li B, Comai L (Sep 2000). "Functional interaction between Ku and the werner syndrome protein in DNA end processing" . The Journal of Biological Chemistry . 275 (37): 28349– 52. doi :10.1074/jbc.C000289200 PMID 10880505 .
Further reading
External links
PDBe-KB provides an overview of all the structure information available in the PDB for Human X-ray repair cross-complementing protein 6
