Connecting the Dots: Interplay between Ubiquitylation and SUMOylation at DNA Double-Strand Breaks

Protein modifications, including phosphorylation, ubiquitylation, and SUMOylation, have emerged as essential components of the response to DNA double-strand breaks (DSBs). Mutations within the genes encoding effectors of these components lead to genomic instability and in selected cases, human radiosensitivity and cancer susceptibility syndromes. In this review, we highlight recent advances in the study of DSB-associated signaling events by ubiquitylation and SUMOylation and discuss how coordination among protein modification systems integrates components of the DNA damage response into a network that regulates DNA repair and transcriptional processes on contiguous stretches of chromatin.