Journal
CELL CYCLE
Volume 11, Issue 6, Pages 1062-1069Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.11.6.19446
Keywords
p97/VCP; DNA double-strand breaks; DNA damage response; DNA repair; Lys48 ubiquitin chain; ubiquitin-proteasome system; genome stability
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Funding
- Forschungskredit of the University of Zurich, Novartis foundation for Biomedical research
- SwissLife foundation
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RNF8/RNF168-dependent Lys63-linked polyubiquitination at sites of DNA double-strand breaks (DSBs) was originally regarded as the sole ubiquitin-signaling pathway involved in the DNA damage response (DDR). However, ubiquitin-dependent p97/VCP segregase activity and RNF8-dependent Lys48-linked polyubiquitin chains at DSB sites have recently been identified as components of an additional and parallel ubiquitin-signaling DDR pathway. This newly identified pathway is essential to spatiotemporal protein turnover and regulates both main branches of DSB repair, homologous recombination and nonhomologous end joining. In this report, the function of the RNF8/Lys48 polyubiquitin chains/p97 pathway is discussed in the context of DSB repair and p97 chromatin-related functions.
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