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Structural aspects of multi-domain RING/Ubox E3 ligases in DNA repair
Authors:Richard G. Hibbert  Francesca Mattiroli  Titia K. Sixma
Affiliation:1. Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, The University of Medicine and Dentistry of New Jersey, 675 Hoes Lane West, Piscataway, NJ 08855, USA;2. Pestka Biomedical Laboratories, 131 Ethel Road West, Suite 6, Piscataway, NJ 08854, USA;1. Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK;2. Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK;3. Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK;1. Chemistry Synthesis and Pollution Control Key Laboratory of Sichuan Province, College of Chemistry and Chemical Engineering, China West Normal University, Nanchong 637009, Sichuan Province, PR China;2. State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China;3. Institute of Biochemistry and Pathobiochemistry, Faculty of Medicine, System Biochemistry, Ruhr-University Bochum, D-44780 Bochum, Germany;4. Department of Biochemistry and Functional Proteomics, Faculty of Biology and BIOSS Centre for Biological Signaling Studies, University of Freiburg, D-79104 Freiburg, Germany;6. the European Molecular Biology Laboratory at Hamburg, D-22607 Hamburg, Germany;5. Department of Biochemistry, Eötvös Loránd University, H-1117 Budapest, Hungary;12. Biaffin GmbH and Co., KG, D-34132 Kassel, Germany
Abstract:Ubiquitin conjugation plays critical roles in virtually all DNA repair pathways. This review provides an overview of the known multi-domain RING/Ubox E3 ligases and their domain structures. An analysis of known RING/Ubox X-ray and NMR structures leads to a discussion of the effects of dimerization. Structural and mechanistic data relating to the E3 ligase preferences for E2 interaction and chain-type specificity are reviewed and the role of the E3 ligases in regulation of the repair pathways is discussed.
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