Endogenous metabolites, environmental agents, and therapeutic drugs promote formation of covalent DNA-protein crosslinks (DPCs). Persistent DPCs compromise genome integrity and are eliminated by multiple repair pathways. It remains obscure how cells choose between diverse mechanisms of DPC repair. Using the yeast S. cerevisiae as a model, Françoise Stutz’s group shows that the post-translational modification SUMO orchestrates multiple alternative DNA-protein crosslink repair pathways. Genetic and biochemical analyses show that SUMO can either promote or inhibit DPC repair. These findings reveal that SUMO tunes available pathways to facilitate faithful DPC repair and genome stability.

The article was published in Cell Reports on Nov. 25, 2021.