title: A novel destruction sequence targets the meiotic regulator Spo13 for anaphase-promoting complex-dependent degradation in anaphase I.
abstract: The anaphase-promoting complex (APC) or cyclosome is a multisubunit ubiquitin-protein ligase that ubiquitinates and thereby promotes the destruction of the mitotic cyclins and the separase inhibitor, securin. The contributions of the APC to progression through the meiotic program are not clear. To clarify the function of the APC in meiosis, we screened several yeast meiotic proteins as APC substrates in vitro. We found that the meiotic regulator Spo13 is an APC substrate that is degraded during anaphase I. Spo13 is expressed only in meiotic cells, where it has multiple functions, including the promotion of monopolar chromosome attachment in the first division. Spo13 ubiquitination by the APC depends on an LxExxxN sequence (residues 26-32) that is distinct from previously described destruction sequences of APC substrates. Mutation of one residue, leucine 26, prevented Spo13 ubiquitination by the APC in vitro and stabilized the protein through the meiotic divisions. Analysis of meiotic progression and spore viability of yeast containing the stabilized Spo13 mutant revealed no significant defects, indicating that Spo13 destruction in anaphase I is not essential for meiosis. We propose that Spo13 destruction is one of multiple mechanisms underlying the switch from monopolar to bipolar chromosome attachment between the meiotic divisions.
authors.affiliation: Department of Physiology, University of California, San Francisco, California 94158, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: Sullivan
authors.forename: David O
authors.initials: DO
authors.lastname: Morgan
mesh_terms: D019943:Amino Acid Substitution; D000705:Anaphase / Q000502:physiology*; D064173:Anaphase-Promoting Complex-Cyclosome; D015825:Chromosomes, Fungal / Q000235:genetics / Q000378:metabolism; D008540:Meiosis / Q000502:physiology*; D020125:Mutation, Missense; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013172:Spores, Fungal / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism*
chemical_list: C097192:SPO13 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome