From Wikipedia, the free encyclopedia
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] Mutant mice deficient in Ku70 exhibit early aging.
[9] 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.
[10] (Also see
DNA damage theory of aging .)
Clinical
A mutation in this gene has been described in a set of 24 families with
autism .
[11] While this is suggestive that this gene may play a role in the development of autism, further investigation is required.
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] and
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