期刊
FRONTIERS IN BIOSCIENCE-LANDMARK
卷 21, 期 -, 页码 514-527出版社
FRONTIERS IN BIOSCIENCE INC
DOI: 10.2741/4406
关键词
Ku70; Ku80; Degradation; Double strand break; NEDD8; Non-homologous end-joining; NHEJ; SCF; RNF8; Proteasome; Ubiquitylation; Review
资金
- Danish Council for Independent Research (Natural Sciences) [12-128803]
- Danish Cancer Society
- Lundbeck Foundation
- Fru Astrid Thaysens Legat for Laegevidenskabelig Grundforskning [ALT 14/01]
- Else og Mogens Wedell - Wedellsborgs Fond [27-15-1]
- Arvid Nilssons Fond
- Fabrikant Ejner Willumsens Mindelegat
- Nordea-Fonden
- Danish Council for Independent Research (Health and Disease) [12-125862]
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-CullinF-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.
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