The Ku70/80 ring in Non-Homologous End-joining: Easy to slip on, hard to remove

Birthe B. Kragelund, Eric - Weterings, Rasmus Hartmann-Petersen, Guido Keijzers

Research output: Contribution to journalReview article

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)514-527
Number of pages14
JournalFrontiers in Bioscience - Landmark
Volume21
Issue number3
StatePublished - Jan 1 2016

Fingerprint

Joining
DNA Repair
Ubiquitin
Repair
DNA
Cullin Proteins
DNA Breaks
Ubiquitin-Protein Ligases
Double-Stranded DNA Breaks
Cell Aging
Ubiquitination
Proteasome Endopeptidase Complex
Degradation
Chromatin
Cell Cycle
Carcinogenesis
Cell Death
Proteins
Cell death
Cells

Keywords

  • Degradation
  • Double strand break
  • Ku70
  • Ku80
  • NEDD8
  • NHEJ
  • Non-homologous endjoining
  • Proteasome
  • Review
  • RNF8
  • SCF
  • Ubiquitylation

ASJC Scopus subject areas

  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

The Ku70/80 ring in Non-Homologous End-joining : Easy to slip on, hard to remove. / Kragelund, Birthe B.; Weterings, Eric -; Hartmann-Petersen, Rasmus; Keijzers, Guido.

In: Frontiers in Bioscience - Landmark, Vol. 21, No. 3, 01.01.2016, p. 514-527.

Research output: Contribution to journalReview article

Kragelund, BB, Weterings, E, Hartmann-Petersen, R & Keijzers, G 2016, 'The Ku70/80 ring in Non-Homologous End-joining: Easy to slip on, hard to remove', Frontiers in Bioscience - Landmark, vol. 21, no. 3, pp. 514-527.
Kragelund, Birthe B. ; Weterings, Eric - ; Hartmann-Petersen, Rasmus ; Keijzers, Guido. / The Ku70/80 ring in Non-Homologous End-joining : Easy to slip on, hard to remove. In: Frontiers in Bioscience - Landmark. 2016 ; Vol. 21, No. 3. pp. 514-527.
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