Abstract
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.
MeSH Terms
Anaphase/physiology
Cell Cycle Proteins/metabolism
Chromosomal Proteins, Non-Histone
Chromosome Segregation/physiology
Chromosomes, Fungal/genetics,metabolism
Endopeptidases/metabolism
Enzyme Activation
Fungal Proteins
Microtubules/metabolism
Mitosis/physiology
Nuclear Proteins/metabolism
Phosphorylation
Protein Tyrosine Phosphatases/metabolism
Saccharomyces cerevisiae/cytology,enzymology,metabolism
Saccharomyces cerevisiae Proteins/metabolism
Separase
Spindle Apparatus/physiology
Chemicals
CDC14 protein, S cerevisiae
Cell Cycle Proteins
Chromosomal Proteins, Non-Histone
Fungal Proteins
Nuclear Proteins
Saccharomyces cerevisiae Proteins
cohesins
Protein Tyrosine Phosphatases
Endopeptidases
TEV protease
ESP1 protein, S cerevisiae
Separase
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Higuchi Toru
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
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