Phospho-regulation of the Shugoshin - Condensin interaction at the centromere in budding yeast
| Autor: | Jennifer Röhrl, Zuzana Storchova, Stephan Gruber, Karolina Peplowska, Young-Min Soh, Frank Bürmann, Yehui Wu, Galal Yahya Metwaly |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
Condensin Amino Acid Motifs Yeast and Fungal Models QH426-470 Biochemistry Spindle pole body Chromosome segregation 0302 clinical medicine Medicine and Health Sciences 570 Biowissenschaften Biologie Drug Interactions Protein Phosphatase 2 Cell Cycle and Cell Division Phosphorylation Post-Translational Modification Genetics (clinical) Adenosine Triphosphatases Centromeres 0303 health sciences biology Kinetochore Chromosome Biology Nuclear Proteins Eukaryota Cell biology DNA-Binding Proteins Spindle checkpoint Experimental Organism Systems Cell Processes Protein Binding Research Article Chromosome Structure and Function Saccharomyces cerevisiae Proteins Biorientation Centromere Immunoblotting Molecular Probe Techniques Mitosis Saccharomyces cerevisiae macromolecular substances Protein Serine-Threonine Kinases Research and Analysis Methods Chromosomes 03 medical and health sciences Condensin complex Saccharomyces Model Organisms ddc:570 Genetics Molecular Biology Techniques Molecular Biology Ecology Evolution Behavior and Systematics 030304 developmental biology Adenosine Triphosphatases/metabolism Centromere/metabolism DNA-Binding Proteins/metabolism Multiprotein Complexes/metabolism Nuclear Proteins/chemistry Nuclear Proteins/genetics Nuclear Proteins/metabolism Protein Phosphatase 2/metabolism Protein Serine-Threonine Kinases/metabolism Saccharomyces cerevisiae Proteins/chemistry Saccharomyces cerevisiae Proteins/genetics Saccharomyces cerevisiae Proteins/metabolism Pharmacology Cohesin Organisms Fungi Biology and Life Sciences Proteins Cell Biology Yeast Spindle apparatus Multiprotein Complexes biology.protein Animal Studies 030217 neurology & neurosurgery |
| Zdroj: | PLoS genetics, vol. 16, no. 8, pp. e1008569 PLoS Genetics PLoS Genetics, Vol 16, Iss 8, p e1008569 (2020) |
| Popis: | Correct bioriented attachment of sister chromatids to the mitotic spindle is essential for chromosome segregation. In budding yeast, the conserved protein shugoshin (Sgo1) contributes to biorientation by recruiting the protein phosphatase PP2A-Rts1 and the condensin complex to centromeres. Using peptide prints, we identified a Serine-Rich Motif (SRM) of Sgo1 that mediates the interaction with condensin and is essential for centromeric condensin recruitment and the establishment of biorientation. We show that the interaction is regulated via phosphorylation within the SRM and we determined the phospho-sites using mass spectrometry. Analysis of the phosphomimic and phosphoresistant mutants revealed that SRM phosphorylation disrupts the shugoshin–condensin interaction. We present evidence that Mps1, a central kinase in the spindle assembly checkpoint, directly phosphorylates Sgo1 within the SRM to regulate the interaction with condensin and thereby condensin localization to centromeres. Our findings identify novel mechanisms that control shugoshin activity at the centromere in budding yeast. Author summary Proper chromosome segregation in eukaryotes is ensured through correct attachment of the spindle microtubules to the centromeric chromosomal regions. The attachment is mediated via the multimolecular proteinaceous complex called the kinetochore. This enables the establishment of bioirentation, when each sister chromatid is attached to microtubules emanating from opposite spindle poles. Shugoshin (Sgo1) is a conserved centromeric protein that facilitates biorientation through its interactions with the protein phosphatase PP2A-Rts1, chromosome passenger complex and centromeric condensin. Here, we identified a serine-rich motif that is required for the interaction of shugoshin with the condensin complex. We show that loss of this region impairs condensin enrichment at the centromere, chromosome biorientation, segregation as well as the function of the chromosome passenger complex in the error correction. Moreover, the interaction is phosphoregulated, as phosphorylation of the serine-rich motif on Sgo1 disrupts its interaction with condensin. Finally, we show that the conserved spindle assembly checkpoint kinase Mps1 is responsible for this phosphorylation. Our findings uncover novel regulatory mechanisms that facilitate proper chromosome segregation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|