title: Ubiquitylation, neddylation and the DNA damage response.
abstract: Failure of accurate DNA damage sensing and repair mechanisms manifests as a variety of human diseases, including neurodegenerative disorders, immunodeficiency, infertility and cancer. The accuracy and efficiency of DNA damage detection and repair, collectively termed the DNA damage response (DDR), requires the recruitment and subsequent post-translational modification (PTM) of a complex network of proteins. Ubiquitin and the ubiquitin-like protein (UBL) SUMO have established roles in regulating the cellular response to DNA double-strand breaks (DSBs). A role for other UBLs, such as NEDD8, is also now emerging. This article provides an overview of the DDR, discusses our current understanding of the process and function of PTM by ubiquitin and NEDD8, and reviews the literature surrounding the role of ubiquitylation and neddylation in DNA repair processes, focusing particularly on DNA DSB repair.
authors.affiliation: The Wellcome Trust and Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK.
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Brown
authors.affiliation: The Wellcome Trust and Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK s.jackson@gurdon.cam.ac.uk.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Jackson
mesh_terms: D004247:DNA / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D008957:Models, Genetic; D000075687:NEDD8 Protein; D011499:Protein Processing, Post-Translational; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination; D014452:Ubiquitins / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; D014452:Ubiquitins; D004247:DNA; D044767:Ubiquitin-Protein Ligases
keywords: DNA damage response; MLN4924; NEDD8; double-strand break repair; ubiquitin
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