The ubiquitin- and SUMO-dependent signaling response to DNA double-strand breaks

► DNA double-strand breaks (DSBs) trigger protein recruitment to DSB-flanking chromatin. ► Non-proteolytic ubiquitylation plays a key regulatory role in promoting this response. ► The RNF8/RNF168 E3 ligase cascade catalyzes DSB-associated chromatin ubiquitylation. ► Ubiquitin and SUMO co-regulate the DSB response by poorly understood mechanisms. ► Recent findings on how ubiquitin and SUMO orchestrate responses to DSBs are discussed.