Ku (protein)

X-ray repair
cross-complementing 5
Crystal structure of human Ku bound to DNA. Ku70 is shown in purple, Ku80 in blue, and the DNA strand in green.[1]
Identifiers
Symbol XRCC5
Alt. symbols Ku80
Entrez 7520
HUGO 12833
OMIM 194364
PDB 1JEY
RefSeq NM_021141
UniProt P13010
Other data
Locus Chr. 2 q35
X-ray repair
cross-complementing 6
Identifiers
Symbol XRCC6
Alt. symbols Ku70, G22P1
Entrez 2547
HUGO 4055
OMIM 152690
PDB 1JEY
RefSeq NM_001469
UniProt P12956
Other data
Locus Chr. 22 q11-q13

Ku is a protein that binds to DNA double-strand break ends and is required for the non-homologous end joining (NHEJ) pathway of DNA repair. Ku is evolutionarily conserved from bacteria to human. The ancestral bacterial Ku is a homodimer (two copies of the same protein bound to each other).[2] Eukaryotic Ku is a heterodimer of two polypeptides, Ku70 (XRCC6) and Ku80 (XRCC5), so named because the molecular weight of the human Ku proteins is around 70 kDa and 80 kDa. The two Ku subunits form a basket-shaped structure that threads onto the DNA end.[1] Once bound, Ku can slide down the DNA strand, allowing more Ku molecules to thread onto the end. In higher eukaryotes, Ku forms a complex with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to form the full DNA-dependent protein kinase, DNA-PK.[3] Ku is thought to function as a molecular scaffold to which other proteins involved in NHEJ can bind.

Both subunits of Ku have been experimentally knocked out in mice. These mice exhibit chromosomal instability, indicating that NHEJ is important for genome maintenance.[4][5]

In many organisms, Ku has additional functions at telomeres in addition to its role in DNA repair.[6]

Abundance of Ku80 seems to be related to species longevity.[7]

References

  1. ^ a b PDB 1JEY; Walker JR, Corpina RA, Goldberg J (August 2001). "Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair". Nature 412 (6847): 607–14. doi:10.1038/35088000. PMID 11493912. 
  2. ^ Doherty AJ, Jackson SP, Weller GR (July 2001). "Identification of bacterial homologues of the Ku DNA repair proteins". FEBS Lett. 500 (3): 186–8. doi:10.1016/S0014-5793(01)02589-3. PMID 11445083. 
  3. ^ Carter T, Vancurová I, Sun I, Lou W, DeLeon S (December 1990). "A DNA-activated protein kinase from HeLa cell nuclei". Mol. Cell. Biol. 10 (12): 6460–71. PMC 362923. PMID 2247066. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=362923. 
  4. ^ Difilippantonio MJ, Zhu J, Chen HT, Meffre E, Nussenzweig MC, Max EE, Ried T, Nussenzweig A (March 2000). "DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation". Nature 404 (6777): 510–4. doi:10.1038/35006670. PMID 10761921. 
  5. ^ Ferguson DO, Sekiguchi JM, Chang S, Frank KM, Gao Y, DePinho RA, Alt FW (June 2000). "The nonhomologous end-joining pathway of DNA repair is required for genomic stability and the suppression of translocations". Proc. Natl. Acad. Sci. U.S.A. 97 (12): 6630–3. doi:10.1073/pnas.110152897. PMC 18682. PMID 10823907. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=18682. 
  6. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1170529. 
  7. ^ Lorenzini A, Johnson FB, Oliver A, Tresini M, Smith JS, Hdeib M, Sell C, Cristofalo VJ, Stamato TD (Nov-Dec 2009). "Significant Correlation of Species Longevity with DNA Double Strand Break-Recognition but not with Telomere Length". Mech Ageing Dev. 130 (11–12): 784–92. doi:10.1016/j.mad.2009.10.004. PMC 2799038. PMID 19896964. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2799038.