title: The Ku70/80 ring in Non-Homologous End-Joining: easy to slip on, hard to remove.
abstract: Non-homologous end-joining (NHEJ) is an essential DNA double strand break repair pathway during all cell cycle stages. Deficiency in NHEJ factors can lead to accumulation of unrepaired DNA breaks or faulty DNA repair, which may ultimately result in cell death, senescence or carcinogenesis. The Ku70/80 heterodimer is a key-player in the NHEJ pathway and binds to DNA termini with high affinity, where it helps to protect DNA ends from degradation and to recruit other NHEJ factors required for repair. The mechanism of Ku70/80 detachment from the DNA helix after completion of DNA repair is incompletely understood. Some data suggest that certain DNA repair factors are ubiquitylated and targeted for proteasomal degradation after repair. Recent studies suggest that Ku80 is conjugated to lysine48-linked ubiquitin chains by the Skp1-Cullin-F-box (SCF) complex and/or the RING finger protein 8 (RNF8) ubiquitin-protein ligases, followed by rapid proteasomal degradation. In this review we address the structure and function of the Ku70/80 heterodimer and how ubiquitylation may affect the release of Ku70/80 from chromatin and its subsequent degradation via the ubiquitin-proteasome system.
authors.affiliation: Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark.
authors.forename: Birthe B
authors.initials: BB
authors.lastname: Kragelund
authors.affiliation: Department of Radiation Oncology, University of Arizona, 1501 N. Campbell Ave, Tucson, Arizona 85724, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Weterings
authors.affiliation: Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Hartmann-Petersen
authors.affiliation: Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark, guido@sund.ku.dk.
authors.forename: Guido
authors.initials: G
authors.lastname: Keijzers
mesh_terms: D034961:Antigens, Nuclear / Q000502:physiology*; D004249:DNA Damage; D059766:DNA End-Joining Repair; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000502:physiology*; D000072200:Ku Autoantigen; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D044767:Ubiquitin-Protein Ligases; D000072200:Ku Autoantigen