Ku (protein)

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Crystal structure of human Ku bound to DNA. Ku70 is shown in purple, Ku80 in blue, and the DNA strand in green.
Crystal structure of human Ku bound to DNA. Ku70 is shown in purple, Ku80 in blue, and the DNA strand in green.

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).[1] Eukaryotic Ku is a heterodimer of two polypeptides, Ku70 and Ku80, 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.[2] 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 knocked out in mouse. 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]

[edit] References

  1. ^ Doherty AJ, Jackson SP, Weller GR. Identification of bacterial homologues of the Ku DNA repair proteins. FEBS Lett. 2001 Jul 6;500(3):186-8. PMID 11445083.
  2. ^ Walker JR, Corpina RA, Goldberg J. Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair. Nature. 2001 Aug 9;412(6847):607-14. PMID 11493912
  3. ^ Carter T, Vancurova I, Sun I, Lou W, DeLeon S. A DNA-activated protein kinase from HeLa cell nuclei. Mol Cell Biol. 1990 Dec;10(12):6460-71. PMID 2247066
  4. ^ Difilippantonio MJ, Zhu J, Chen HT, Meffre E, Nussenzweig MC, Max EE, Ried T, Nussenzweig A. DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation. Nature. 2000 Mar 30;404(6777):510-4. PMID 1076192
  5. ^ Ferguson DO, Sekiguchi JM, Chang S, Frank KM, Gao Y, DePinho RA, Alt FW. 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. 2000 Jun 6;97(12):6630-3. PMID 10823907
  6. ^ Boulton SJ, Jackson SP. 1998. Components of the Ku-dependent non-homologous endjoining pathway are involved in telomeric length maintenance and telomeric silencing. EMBO J. 17:1819–28 PMID 9501103
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