title: Degradation-linked ubiquitin signal and proteasome are integral components of DNA double strand break repair: New perspectives for anti-cancer therapy.
abstract: Damaged DNA leads to genomic instability that causes many diseases such as cancer. Cells evolved the DNA damage response (DDR), which recognizes and efficiently repairs damaged DNA through the action of highly coordinated signalling mechanisms. Recently, a non-degradation-linked Lys(K)63-ubiquitin signal emerged as a signalling pathway essential for orchestration of the DDR after DNA double strand breaks (DSBs). How the ubiquitin-dependent proteasomal degradation system (UPS) coordinates DDR after DSBs is still poorly understood. Here, we review the evidence, suggesting the involvement of the degradation-linked K48-ubiquitin signal and the proteasome at the sites of DSBs. Based on this we propose the UPS as a central element in the orchestration of the DDR at the sites of DSBs. The suggested model is also discussed in the context of anti-cancer therapy.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zürich-Vetsuisse, Winterthurerstrasse 260, Zürich CH-8057, Switzerland. kristijan.ramadan@vetpharm.uzh.ch
authors.forename: Kristijan
authors.initials: K
authors.lastname: Ramadan
authors.forename: Mayura
authors.initials: M
authors.lastname: Meerang
mesh_terms: D000818:Animals; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D011480:Protease Inhibitors / Q000627:therapeutic use; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D001897:Boronic Acids; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D025801:Ubiquitin; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex