title: Fin1-PP1 Helps Clear Spindle Assembly Checkpoint Protein Bub1 from Kinetochores in Anaphase.
abstract: The spindle assembly checkpoint (SAC) monitors chromosome attachment defects, and the assembly of SAC proteins at kinetochores is essential for its activation, but the SAC disassembly process remains unknown. We found that deletion of a 14-3-3 protein, Bmh1, or hyperactivation of Cdc14 early anaphase release (FEAR) allows premature SAC silencing in budding yeast, which depends on a kinetochore protein Fin1 that forms a complex with protein phosphatase PP1. Previous works suggest that FEAR-dependent Fin1 dephosphorylation promotes Bmh1-Fin1 dissociation, which enables kinetochore recruitment of Fin1-PP1. We found persistent kinetochore association of SAC protein Bub1 in fin1Δ mutants after anaphase entry. Therefore, we revealed a mechanism that clears SAC proteins from kinetochores. After anaphase entry, FEAR activation promotes kinetochore enrichment of Fin1-PP1, resulting in SAC disassembly at kinetochores. This mechanism is required for efficient SAC silencing after SAC is challenged, and untimely Fin1-kinetochore association causes premature SAC silencing and chromosome missegregation.
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Florida State University, 1115 West Call Street, Tallahassee, FL 32306-4300, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bokros
authors.affiliation: Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Curtis
authors.initials: C
authors.lastname: Gravenmier
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Florida State University, 1115 West Call Street, Tallahassee, FL 32306-4300, USA.
authors.forename: Fengzhi
authors.initials: F
authors.lastname: Jin
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Florida State University, 1115 West Call Street, Tallahassee, FL 32306-4300, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Richmond
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Florida State University, 1115 West Call Street, Tallahassee, FL 32306-4300, USA. Electronic address: yanchang.wang@med.fsu.edu.
authors.forename: Yanchang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000705:Anaphase; D020090:Chromosome Segregation; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D020868:Gene Silencing; D018386:Kinetochores / Q000378:metabolism*; D059566:M Phase Cell Cycle Checkpoints; D050296:Microbial Viability; D009154:Mutation / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: C584280:Bub1 protein, S cerevisiae; D003598:Cytoskeletal Proteins; C456282:FIN1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D017346:Protein Serine-Threonine Kinases
keywords: Bmh1; FEAR pathway; Fin1; PP1; spindle assembly checkpoint
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