title: An Alternatively Spliced Bifunctional Localization Signal Reprograms Human Shugoshin 1 to Protect Centrosomal Instead of Centromeric Cohesin.
abstract: Separation of human sister chromatids involves the removal of DNA embracing cohesin ring complexes. Ring opening occurs by prophase-pathway-dependent phosphorylation and separase-mediated cleavage, with the former being antagonized at centromeres by Sgo1-dependent PP2A recruitment. Intriguingly, prophase pathway signaling and separase's proteolytic activity also bring about centriole disengagement, whereas Sgo1 is again counteracting this licensing step of later centrosome duplication. Here, we demonstrate that alternative splice variants of human Sgo1 specifically and exclusively localize and function either at centromeres or centrosomes. A small C-terminal peptide encoded by exon 9 of SGO1 (CTS for centrosomal targeting signal of human Sgo1) is necessary and sufficient to drive centrosomal localization and simultaneously abrogate centromeric association of corresponding Sgo1 isoforms. Cohesin is shown to be a target of the prophase pathway at centrosomes and protected by Sgo1-PP2A. Accordingly, premature centriole disengagement in response to Sgo1 depletion is suppressed by blocking ring opening of an engineered cohesin.
authors.affiliation: Department of Genetics, University of Bayreuth, 95444 Bayreuth, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Mohr
authors.affiliation: Department of Genetics, University of Bayreuth, 95444 Bayreuth, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Buheitel
authors.affiliation: Department of Genetics, University of Bayreuth, 95444 Bayreuth, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Schöckel
authors.affiliation: Department of Genetics, University of Bayreuth, 95444 Bayreuth, Germany.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Karalus
authors.affiliation: Department of Genetics, University of Bayreuth, 95444 Bayreuth, Germany; Annikki GmbH, 8020 Graz, Austria.
authors.forename: Bernd
authors.initials: B
authors.lastname: Mayer
authors.affiliation: Department of Genetics, University of Bayreuth, 95444 Bayreuth, Germany. Electronic address: olaf.stemmann@uni-bayreuth.de.
authors.forename: Olaf
authors.initials: O
authors.lastname: Stemmann
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002502:Centrioles / Q000378:metabolism / Q000648:ultrastructure; D002503:Centromere / Q000378:metabolism / Q000648:ultrastructure; D018385:Centrosome / Q000378:metabolism / Q000648:ultrastructure; D002842:Chromatids / Q000378:metabolism / Q000648:ultrastructure; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D005091:Exons; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011418:Prophase; D011485:Protein Binding; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism*; D021382:Protein Sorting Signals / Q000235:genetics*; D021381:Protein Transport; D059748:Proteolysis; D015398:Signal Transduction; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D054648:Protein Phosphatase 2; D021382:Protein Sorting Signals; D000097722:Cohesins; C496644:SGO1 protein, human; C517189:PPP2CA protein, human