blm3-1 Is an Allele of UBP3, a Ubiquitin Protease that Appears to Act During Transcription of Damaged DNA

Yeast Blm10 and mammalian PA200 proteins share significant sequence similarity and both cap the ends of 20 S proteasomes and enhance degradation of some peptide substrates. Blm10 was identified as a suppressor of the yeast blm3-1 mutation, and initially was thought to be the Blm3 protein. Both the blm3-1 and blm10-Δ mutations were reported to cause sensitivity to bleomycin and other forms of DNA damage, suggesting a role for Blm10/PA200–proteasome complexes in DNA repair. We have been unable to observe significant DNA damage sensitivity in blm10-Δ mutants in several genetic backgrounds, and we have therefore further investigated the relationship between BLM10 and blm3-1. We find that blm3-1 is a nonsense mutation in the ubiquitin protease gene UBP3. Deleting UBP3 causes phenotypes similar to those caused by blm3-1, but neither causes a general defect in DNA repair. Ubp3 has several known functions, and genetic interaction data presented here suggest an additional role in transcriptional elongation. The phenotypes caused by blm3-1 and ubp3-Δ mutations are not suppressed by over-expression of BLM10, nor are they affected by deletion of BLM10. These results remove key components of the previously reported connection between Blm10/PA200–proteasome complexes and DNA repair, and they suggest a novel way to interpret sensitivity to bleomycin as resulting from defects in transcription elongation.