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RNF4 interacts with both SUMO and nucleosomes to promote the DNA damage response |
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| Authors: | Lynda M Groocock Minghua Nie John Prudden Davide Moiani Tao Wang Anton Cheltsov Robert P Rambo Andrew S Arvai Chiharu Hitomi John A Tainer Karolin Luger J Jefferson P Perry Eros Lazzerini‐Denchi Michael N Boddy |
| Institution: | 1. Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA, USA;2. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA;3. Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, Colorado State University, Fort Collins, CO, USA;4. Q‐MOL L.L.C., San Diego, CA, USA;5. Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA;6. Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kollam, Kerala, India;7. Department of Molecular & Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA |
| Abstract: | The post‐translational modification of DNA repair and checkpoint proteins by ubiquitin and small ubiquitin‐like modifier (SUMO) critically orchestrates the DNA damage response (DDR). The ubiquitin ligase RNF4 integrates signaling by SUMO and ubiquitin, through its selective recognition and ubiquitination of SUMO‐modified proteins. Here, we define a key new determinant for target discrimination by RNF4, in addition to interaction with SUMO. We identify a nucleosome‐targeting motif within the RNF4 RING domain that can bind DNA and thereby enables RNF4 to selectively ubiquitinate nucleosomal histones. Furthermore, RNF4 nucleosome‐targeting is crucially required for the repair of TRF2‐depleted dysfunctional telomeres by 53BP1‐mediated non‐homologous end joining. |
| Keywords: | RNF4 SUMO‐targeted E3 ubiquitin ligase (STUbL) small ubiquitin‐like modifier telomere ubiquitin |