title: DNA damage emergency: cellular garbage disposal to the rescue?
abstract: The proteasome is a cellular machine found in the cytosol, nucleus and on chromatin that performs much of the proteolysis in eukaryotic cells. Recent reports show it is enriched at sites of double-stranded DNA breaks (DSBs) in mammalian cells. What is it doing there? This review will address three possibilities suggested by recent reports: in degrading proteins after their ubiquitination at and eviction from chromatin; as a deubiquitinase, specific to the antagonism of ubiquitin conjugates generated as part of the signalling of a DSB; and as a functional component of DNA repair mechanism itself. These findings add complexity to the proteasome as a potential therapeutic target in cancer treatment.
authors.affiliation: School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK.
authors.forename: H R
authors.initials: HR
authors.lastname: Stone
authors.affiliation: School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK.
authors.forename: J R
authors.initials: JR
authors.lastname: Morris
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002843:Chromatin / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D061988:Proteasome Inhibitors / Q000627:therapeutic use; D054875:Ubiquitination
chemical_list: D000970:Antineoplastic Agents; D002843:Chromatin; D004268:DNA-Binding Proteins; D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex