title: The Bre5/Ubp3 ubiquitin protease complex from budding yeast contributes to the cellular response to DNA damage.
abstract: The ubiquitination status of proteins can control numerous aspects of protein function through targeted destruction or by altering protein-protein interactions, subcellular localization, or enzymatic activity. In addition to enzymes that mediate the conjugation of ubiquitin moieties to target proteins, there are enzymes that catalyze the removal of ubiquitin, termed ubiquitin proteases. One such ubiquitin protease, Ubp3, exists in a complex with a partner protein: Bre5. This complex has been implicated in a variety of cellular activities, and was recently identified in large-scale screens for genetic interactions with known components of the DNA damage response pathway. We found that this complex plays a role in the cellular response to the DNA damaging agent phleomycin and strains lacking the complex have a defect in non-homologous end joining. Although this complex is also important for telomeric silencing, maintenance of the cell wall, and global transcriptional regulation, we present evidence suggesting that the role of this complex in DNA damage responses is distinct from these other roles. First, we found that Ubp3/Bre5 functions antagonistically with Bul1 in DNA damage responses, but not in its other cellular functions. Additionally, we have generated mutants of Bre5 that are specifically defective in DNA damage responses.
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, United Kingdom.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bilsland
authors.forename: Malin
authors.initials: M
authors.lastname: Hult
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bell
authors.forename: Per
authors.initials: P
authors.lastname: Sunnerhagen
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Downs
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002843:Chromatin / Q000378:metabolism; D004249:DNA Damage; D010450:Endopeptidases / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D010957:Plasmids; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C099939:BUL1 protein, S cerevisiae; D002352:Carrier Proteins; D002843:Chromatin; D029701:Saccharomyces cerevisiae Proteins; D044767:Ubiquitin-Protein Ligases; D010450:Endopeptidases; C503886:Bre5 protein, S cerevisiae; C101111:UBP3 protein, S cerevisiae