title: FEAR-mediated activation of Cdc14 is the limiting step for spindle elongation and anaphase progression.
abstract: Cleavage of cohesins and cyclin-dependent kinase (CDK) inhibition are thought to be sufficient for triggering chromosome segregation. Here we identify an essential requirement for anaphase chromosome movement. We show that, at anaphase onset, the phosphatase Cdc14 and the polo-like kinase Cdc5 are redundantly required to drive spindle elongation. This role of Cdc14 is mediated by the FEAR network, a group of proteins that activates Cdc14 at anaphase onset, and we suggest that Cdc5 facilitates both Cdc14 activation and CDK inhibition. We further identify the kinesin-5 motor protein Cin8 as a key target of Cdc14. Indeed, Cin8 mutants lacking critical CDK phosphorylation sites suppress the requirement for Cdc14 and Cdc5 in anaphase spindle elongation. Our results indicate that cohesin dissolution and CDK inhibition per se are not sufficient to drive sister chromatid segregation but that the motor protein Cin8 must be activated to elongate the spindle.
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan 20139, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Roccuzzo
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan 20139, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Visintin
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan 20139, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Tili
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan 20139, Italy.
authors.forename: Rosella
authors.initials: R
authors.lastname: Visintin
mesh_terms: D000705:Anaphase; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002842:Chromatids / Q000378:metabolism / Q000648:ultrastructure; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation; D004789:Enzyme Activation; D015966:Gene Expression Regulation, Fungal; D016547:Kinesins / Q000172:deficiency / Q000235:genetics*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism / Q000648:ultrastructure; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D016547:Kinesins; D017346:Protein Serine-Threonine Kinases; D017027:Protein Tyrosine Phosphatases; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; C074860:CDC14 protein, S cerevisiae; C075342:CIN8 protein, S cerevisiae; C081927:CDC5 protein, S cerevisiae