The 19S regulatory complex of the proteasome functions independently of proteolysis in nucleotide excision repair

The 26S proteasome degrades proteins targeted by the ubiquitin pathway, a f unction thought to explain its role in cellular processes. The proteasome i nteracts with the ubiquitin-like N terminus of Rad23, a nucleotide excision repair (NER) protein, in Saccharomyces cerevisiae. Deletion of the ubiquit in-like domain causes UV radiation sensitivity. Here, we show that the ubiq uitin-like domain of Rad23 is required for optimal activity of an in vitro NER system. Inhibition of proteasomal ATPases diminishes NER activity in vi tro and increases UV sensitivity in vivo. Surprisingly, blockage of protein degradation by the proteasome has no effect on the efficiency of NER. This establishes that the regulatory complex of the proteasome has a function i ndependent of protein degradation.