YPL260W, a high-copy suppressor of a copper-sensitive phenotype in yeast, is linked to DNA repair and proteasome function

• Proteasome mutants are resistant to copper.
• A dominant mutation negating this copper resistance is discovered.
• Four high copy suppressors of this mutation are identified, including YPL260W.
• The first characterization of YPL260W, a highly conserved fungal gene, is presented.
• YPL260W, renamed CUB1, is linked to DNA repair and proteasome function.

The ubiquitin–proteasome system directly impacts the metabolism of heavy metals and yeast has become an important model in understanding this interplay. We demonstrate that yeast mutants with defects in proteasome function are able to tolerate elevated levels of copper. In the course of our analysis, we isolate a yeast mutant that not only negates this copper tolerance in proteasome mutants, but renders yeast exquisitely sensitive to this metal. To better understand the nature of the defect, we carry out a plasmid-based genetic screen to identify high-copy suppressors of this strong copper sensitivity. We identify four genes not previously known to be associated with copper metabolism: CDC53, PSP1, YNL200C, and YPL260W. The latter is a highly conserved fungal gene of no known function. Here, we undertake the first characterization of YPL260W. We demonstrate YPL260W to have a role in bleomycin tolerance with links to DNA repair and proteasome function.