Rad23 links DNA repair to the ubiquitin/proteasome pathway

Abstract

Rad23 is an evolutionarily conserved protein that is important for nucleotide excision repair^1,2,3. A regulatory role has been proposed for Rad23 because rad23 mutants are sensitive to ultraviolet light but are still capable of incising damaged DNA⁴,⁵. Here we show that Rad23 interacts with the 26S proteasome through an amino-terminal ubiquitin-like domain (UbL^R23). The carboxy terminus of Rad23 binds to the Rad4 DNA repair protein and creates a link between the DNA repair and proteasome pathways. The ultraviolet sensitivity caused by deletion of the UbL^R23 domain may therefore arise from its inability to interact with the proteasome. The fusion proteins glutathione S-transferase (GST)–Rad23 and Rad4–haemagglutinin (HA), and the proteasome subunits Cim3 and Cim5, cofractionate through consecutive chromatography steps. The ubiquitin-like domain of human Rad23 (UbL^HRB) also interacts with the human proteasome. These results demonstrate that ubiquitin-like domains (UbLs) represent a new class of proteasome-interacting motifs.