title: The Role of the COP9 Signalosome and Neddylation in DNA Damage Signaling and Repair.
abstract: The maintenance of genomic integrity is an important process in organisms as failure to sense and repair damaged DNA can result in a variety of diseases. Eukaryotic cells have developed complex DNA repair response (DDR) mechanisms to accurately sense and repair damaged DNA. Post-translational modifications by ubiquitin and ubiquitin-like proteins, such as SUMO and NEDD8, have roles in coordinating the progression of DDR. Proteins in the neddylation pathway have also been linked to regulating DDR. Of interest is the COP9 signalosome (CSN), a multi-subunit metalloprotease present in eukaryotes that removes NEDD8 from cullins and regulates the activity of cullin-RING ubiquitin ligases (CRLs). This in turn regulates the stability and turnover of a host of CRL-targeted proteins, some of which have established roles in DDR. This review will summarize the current knowledge on the role of the CSN and neddylation in DNA repair.
authors.affiliation: Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada. dudleyc@dal.ca.
authors.forename: Dudley
authors.initials: D
authors.lastname: Chung
authors.affiliation: Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada. dellaire@dal.ca.|Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS B3H 4R2, Canada. dellaire@dal.ca.
authors.forename: Graham
authors.initials: G
authors.lastname: Dellaire
mesh_terms: D000818:Animals; D000075686:COP9 Signalosome Complex; D004249:DNA Damage / Q000235:genetics / Q000502:physiology*; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D046912:Multiprotein Complexes; D025801:Ubiquitin; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex
keywords: COP9 Signalosome; DNA repair; NEDD8