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PMID: 15650742 Published · ppublish English Journal Article

Stabilization of microtubule dynamics at anaphase onset promotes chromosome segregation.

Nature ·Vol. 433 ·No. 7022 ·2005-01-13 ·Pages 171-6

Higuchi T, Uhlmann F

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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Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
Published
2005-01-13
Pages
171-6
Language
English
Region
England
NLM ID
0410462
PMCID
PMC2586334
Subset
IM
Grants
Cancer Research UK · A3592 · United Kingdom
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