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The Coordination of Centromere Replication, Spindle Formation, and Kinetochore-microtubule Interaction in Budding Yeast

Overview
Journal PLoS Genet
Specialty Genetics
Date 2008 Nov 22
PMID 19023403
Citations 22
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Abstract

The kinetochore is a protein complex that assembles on centromeric DNA to mediate chromosome-microtubule interaction. Most eukaryotic cells form the spindle and establish kinetochore-microtubule interaction during mitosis, but budding yeast cells finish these processes in S-phase. It has long been noticed that the S-phase spindle in budding yeast is shorter than that in metaphase, but the biological significance of this short S-phase spindle structure remains unclear. We addressed this issue by using ask1-3, a temperature-sensitive kinetochore mutant that exhibits partially elongated spindles at permissive temperature in the presence of hydroxyurea (HU), a DNA synthesis inhibitor. After exposure to and removal of HU, ask1-3 cells show a delayed anaphase entry. This delay depends on the spindle checkpoint, which monitors kinetochore-microtubule interaction defects. Overproduction of microtubule-associated protein Ase1 or Cin8 also induces spindle elongation in HU-arrested cells. The spindle checkpoint-dependent anaphase entry delay is also observed after ASE1 or CIN8 overexpression in HU-arrested cells. Therefore, the shorter spindle in S-phase cells is likely to facilitate proper chromosome-microtubule interaction.

Citing Articles

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Cell-cycle phospho-regulation of the kinetochore.

Klemm C, Thorpe P, Olafsson G Curr Genet. 2020; 67(2):177-193.

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Inhibition of spindle extension through the yeast S phase checkpoint is coupled to replication fork stability and the integrity of centromeric DNA.

Julius J, Peng J, McCulley A, Caridi C, Arnak R, See C Mol Biol Cell. 2019; 30(22):2771-2789.

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