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.

Department of Biochemistry and Cell Biology Max F Perutz Laboratories University of Vienna Vienna 1030 Austria

Department of Biology Masaryk University Brno 62500 Czech Republic

Department of Biology Masaryk University Brno 62500 Czech Republic; National Centre for Biomolecular Research Masaryk University Brno 62500 Czech Republic; International Clinical Research Center St Anne's University Hospital in Brno Brno 60200 Czech Republic

Department of Molecular Medicine Institute of Biotechnology University of Texas Health Science Center at San Antonio San Antonio TX 78229 USA

Department of Molecular Medicine Institute of Biotechnology University of Texas Health Science Center at San Antonio San Antonio TX 78229 USA; Division of Radiation Biology Department of Radiation Oncology University of Texas Health Science Center at San Antonio San Antonio TX 78229 USA

Molecular Biology Program Memorial Sloan Kettering Cancer Center New York NY 10065 USA

Molecular Biology Program Memorial Sloan Kettering Cancer Center New York NY 10065 USA; Programs in Biochemistry Cell and Molecular Biology Weill Cornell Graduate School of Medical Sciences New York NY 10065 USA

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Sumoylation influences DNA break repair partly by increasing the solubility of a conserved end resection protein