The DNA repair protein Rad23 is a negative regulator of multi-ubiquitin chain assembly

Rad23 is a nucleotide-excision repair protein with a previously unknown bio chemical function. We determined that yeast and human Rad23 inhibited multi -ubiquitin (Ub) chain formation and the degradation of proteolytic substrat es. Significantly, Rad23 could be cc-precipitated with a substrate that con tained a short multi-Ub chain. The UV sensitivity of rad23 Delta was reduce d in mutants lacking the E2 enzyme Ubc4, or the multi-Db chain-promoting fa ctor Ufd2, These studies suggest that the stability of proteolytic substrat es is governed by the competing action of multi-Db chain-promoting and chai n-inhibiting factors. The stabilization of DNA repair and stress factors co uld represent an important biological function of Rad23.