title: The ubiquitin- and SUMO-dependent signaling response to DNA double-strand breaks.
abstract: DNA double-strand breaks (DSBs) represent the most destructive type of chromosomal lesion and trigger rapid chromatin restructuring accompanied by accumulation of proteins in the vicinity of the DSB. Non-proteolytic ubiquitylation of chromatin surrounding DSBs, mediated by the RNF8/RNF168 ubiquitin ligase cascade, has emerged as a key mechanism for restoration of genome integrity by licensing the DSB-modified chromatin to concentrate genome caretaker proteins such as 53BP1 and BRCA1 near the lesions. In parallel, SUMOylation of upstream DSB regulators is also required for execution of this ubiquitin-dependent chromatin response, but its molecular basis is currently unclear. Here, we discuss recent insights into how ubiquitin- and SUMO-dependent signaling processes cooperate to orchestrate protein interactions with sites of DNA damage to facilitate DSB repair.
authors.affiliation: Ubiquitin Signaling Group, Department of Disease Biology, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark.
authors.forename: Simon
authors.initials: S
authors.lastname: Bekker-Jensen
authors.forename: Niels
authors.initials: N
authors.lastname: Mailand
mesh_terms: D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D008957:Models, Genetic; D015398:Signal Transduction; D058207:Sumoylation; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; C486521:RNF8 protein, human; D025801:Ubiquitin; C535210:RNF168 protein, human; D044767:Ubiquitin-Protein Ligases