Stabilization of microtubule dynamics at anaphase onset promotes chromosome segregation.
Microtubules of the mitotic spindle form the structural basis for chromosome segregation. In metaphase, microtubules show high dynamic instability, which is thought to aid the 'search and capture' of chromosomes for bipolar alignment on the spindle. Microtubules suddenly become more stable at the onset of anaphase, but how this change in microtubule behaviour is regulated and how important it is for the ensuing chromosome segregation are unknown. Here we show that in the budding yeast Saccharomyces cerevisiae, activation of the phosphatase Cdc14 at anaphase onset is both necessary and sufficient for silencing microtubule dynamics. Cdc14 is activated by separase, the protease that triggers sister chromatid separation, linking the onset of anaphase to microtubule stabilization. If sister chromatids separate in the absence of Cdc14 activity, microtubules maintain high dynamic instability; this correlates with defects in both the movement of chromosomes to the spindle poles (anaphase A) and the elongation of the anaphase spindle (anaphase B). Cdc14 promotes localization of microtubule-stabilizing proteins to the anaphase spindle, and dephosphorylation of the kinetochore component Ask1 contributes to both the silencing of microtubule turnover and successful anaphase A.
Higuchi
Toru
T
Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Uhlmann
Frank
F
D000705:Anaphase / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone; D020090:Chromosome Segregation / Q000502:physiology*; D015825:Chromosomes, Fungal / Q000235:genetics / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D004789:Enzyme Activation; D005656:Fungal Proteins; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D064247:Separase; D008941:Spindle Apparatus / Q000502:physiology; D000097722:Cohesins
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D010450:Endopeptidases; D005656:Fungal Proteins; D009687:Nuclear Proteins; D017027:Protein Tyrosine Phosphatases; D029701:Saccharomyces cerevisiae Proteins; D064247:Separase; D000097722:Cohesins; C074860:CDC14 protein, S cerevisiae; C099488:TEV protease; C577986:ESP1 protein, S cerevisiae