Publications

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. Synopsis RNF4 is an important ubiquitin ligase in the DNA damage response (DDR) that targets SUMOylated proteins. This study shows that it also contains a nucleosome-targeting motif that crucially supports the DDR genome-wide. RNF4 promotes ATM-dependent 53BP1 recruitment and repair at dysfunctional telomeres. RNF4 RING domain contains an RNF168 and RING1b-related nucleosome-targeting motif. RNF4 recognizes both SUMO and nucleosomes to support DNA repair. RNF4 is an important ubiquitin ligase in the DNA damage response (DDR) that targets SUMOylated proteins. This study shows that it also contains a nucleosome-targeting motif that crucially supports the DDR genome-wide. © 2014 The Authors.