A Versatile Scaffold Contributes to Damage Survival via Sumoylation and Nuclease Interactions

Abstract

Summary: DNA repair scaffolds mediate specific DNA and protein interactions in order to assist repair enzymes in recognizing and removing damaged sequences. Many scaffold proteins are dedicated to repairing a particular type of lesion. Here, we show that the budding yeast Saw1 scaffold is more versatile. It helps cells cope with base lesions and protein-DNA adducts through its known function of recruiting the Rad1-Rad10 nuclease to DNA. In addition, it promotes UV survival via a mechanism mediated by its sumoylation. Saw1 sumoylation favors its interaction with another nuclease Slx1-Slx4, and this SUMO-mediated role is genetically separable from two main UV lesion repair processes. These effects of Saw1 and its sumoylation suggest that Saw1 is a multifunctional scaffold that can facilitate diverse types of DNA repair through its modification and nuclease interactions. : Scaffold proteins are not DNA repair enzymes themselves but make important contributions to DNA repair by regulating and coordinating various enzymes with their DNA substrates. Sarangi et al. reveal the versatility of the Saw1 scaffold by identifying how it copes with several types of DNA damage that depend on its nuclease interactions and sumoylation. These findings highlight the diverse ways in which multifunctional scaffolds can operate under genotoxic stress and how this is directed by protein modification.