title: Slx5/Slx8 Promotes Replication Stress Tolerance by Facilitating Mitotic Progression.
abstract: Loss of minichromosome maintenance protein 10 (Mcm10) causes replication stress. We uncovered that S. cerevisiae mcm10-1 mutants rely on the E3 SUMO ligase Mms21 and the SUMO-targeted ubiquitin ligase complex Slx5/8 for survival. Using quantitative mass spectrometry, we identified changes in the SUMO proteome of mcm10-1 mutants and revealed candidates regulated by Slx5/8. Such candidates included subunits of the chromosome passenger complex (CPC), Bir1 and Sli15, known to facilitate spindle assembly checkpoint (SAC) activation. We show here that Slx5 counteracts SAC activation in mcm10-1 mutants under conditions of moderate replication stress. This coincides with the proteasomal degradation of sumoylated Bir1. Importantly, Slx5-dependent mitotic relief was triggered not only by Mcm10 deficiency but also by treatment with low doses of the alkylating drug methyl methanesulfonate. Based on these findings, we propose a model in which Slx5/8 allows for passage through mitosis when replication stress is tolerable.
authors.affiliation: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Yee Mon
authors.initials: YM
authors.lastname: Thu
authors.affiliation: University of Minnesota Informatics Institute, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Susan Kaye
authors.initials: SK
authors.lastname: Van Riper
authors.affiliation: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: LeeAnn
authors.initials: L
authors.lastname: Higgins
authors.affiliation: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Tianji
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Jordan Robert
authors.initials: JR
authors.lastname: Becker
authors.affiliation: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Todd William
authors.initials: TW
authors.lastname: Markowski
authors.affiliation: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Hai Dang
authors.initials: HD
authors.lastname: Nguyen
authors.affiliation: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Timothy Jon
authors.initials: TJ
authors.lastname: Griffin
authors.affiliation: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: bieli003@umn.edu.
authors.forename: Anja Katrin
authors.initials: AK
authors.lastname: Bielinsky
mesh_terms: D002846:Chromatography, Affinity; D004249:DNA Damage; D004261:DNA Replication; D017353:Gene Deletion; D042822:Genomic Instability; D059566:M Phase Cell Cycle Checkpoints / Q000235:genetics; D050296:Microbial Viability; D008938:Mitosis; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D055550:Protein Stability; D021122:Protein Subunits / Q000378:metabolism; D059748:Proteolysis; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D013312:Stress, Physiological; D058207:Sumoylation; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; C515574:Slx8 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex; C515573:Slx5 protein, S cerevisiae