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Yeast Kinesin-5 Motor Protein CIN8 Promotes Accurate Chromosome Segregation

Accurate chromosome segregation depends on bipolar chromosome–microtubule attachment and tension generation on chromosomes. Incorrect chromosome attachment results in chromosome missegregation, which contributes to genome instability. The kinetochore is a protein complex that localizes at the centro...

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Autores principales: Sherwin, Delaney, Huetteman, Abigail, Wang, Yanchang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316075/
https://www.ncbi.nlm.nih.gov/pubmed/35883587
http://dx.doi.org/10.3390/cells11142144
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author Sherwin, Delaney
Huetteman, Abigail
Wang, Yanchang
author_facet Sherwin, Delaney
Huetteman, Abigail
Wang, Yanchang
author_sort Sherwin, Delaney
collection PubMed
description Accurate chromosome segregation depends on bipolar chromosome–microtubule attachment and tension generation on chromosomes. Incorrect chromosome attachment results in chromosome missegregation, which contributes to genome instability. The kinetochore is a protein complex that localizes at the centromere region of a chromosome and mediates chromosome–microtubule interaction. Incorrect chromosome attachment leads to checkpoint activation to prevent anaphase onset. Kinetochore detachment activates the spindle assembly checkpoint (SAC), while tensionless kinetochore attachment relies on both the SAC and tension checkpoint. In budding yeast Saccharomyces cerevisiae, kinesin-5 motor proteins Cin8 and Kip1 are needed to separate spindle pole bodies for spindle assembly, and deletion of CIN8 causes lethality in the absence of SAC. To study the function of Cin8 and Kip1 in chromosome segregation, we constructed an auxin-inducible degron (AID) mutant, cin8-AID. With this conditional mutant, we first confirmed that cin8-AID kip1∆ double mutants were lethal when Cin8 is depleted in the presence of auxin. These cells arrested in metaphase with unseparated spindle pole bodies and kinetochores. We further showed that the absence of either the SAC or tension checkpoint was sufficient to abolish the cell-cycle delay in cin8-AID mutants, causing chromosome missegregation and viability loss. The tension checkpoint-dependent phenotype in cells with depleted Cin8 suggests the presence of tensionless chromosome attachment. We speculate that the failed spindle pole body separation in cin8 mutants could increase the chance of tensionless syntelic chromosome attachments, which depends on functional tension checkpoint for survival.
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spelling pubmed-93160752022-07-27 Yeast Kinesin-5 Motor Protein CIN8 Promotes Accurate Chromosome Segregation Sherwin, Delaney Huetteman, Abigail Wang, Yanchang Cells Article Accurate chromosome segregation depends on bipolar chromosome–microtubule attachment and tension generation on chromosomes. Incorrect chromosome attachment results in chromosome missegregation, which contributes to genome instability. The kinetochore is a protein complex that localizes at the centromere region of a chromosome and mediates chromosome–microtubule interaction. Incorrect chromosome attachment leads to checkpoint activation to prevent anaphase onset. Kinetochore detachment activates the spindle assembly checkpoint (SAC), while tensionless kinetochore attachment relies on both the SAC and tension checkpoint. In budding yeast Saccharomyces cerevisiae, kinesin-5 motor proteins Cin8 and Kip1 are needed to separate spindle pole bodies for spindle assembly, and deletion of CIN8 causes lethality in the absence of SAC. To study the function of Cin8 and Kip1 in chromosome segregation, we constructed an auxin-inducible degron (AID) mutant, cin8-AID. With this conditional mutant, we first confirmed that cin8-AID kip1∆ double mutants were lethal when Cin8 is depleted in the presence of auxin. These cells arrested in metaphase with unseparated spindle pole bodies and kinetochores. We further showed that the absence of either the SAC or tension checkpoint was sufficient to abolish the cell-cycle delay in cin8-AID mutants, causing chromosome missegregation and viability loss. The tension checkpoint-dependent phenotype in cells with depleted Cin8 suggests the presence of tensionless chromosome attachment. We speculate that the failed spindle pole body separation in cin8 mutants could increase the chance of tensionless syntelic chromosome attachments, which depends on functional tension checkpoint for survival. MDPI 2022-07-07 /pmc/articles/PMC9316075/ /pubmed/35883587 http://dx.doi.org/10.3390/cells11142144 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sherwin, Delaney
Huetteman, Abigail
Wang, Yanchang
Yeast Kinesin-5 Motor Protein CIN8 Promotes Accurate Chromosome Segregation
title Yeast Kinesin-5 Motor Protein CIN8 Promotes Accurate Chromosome Segregation
title_full Yeast Kinesin-5 Motor Protein CIN8 Promotes Accurate Chromosome Segregation
title_fullStr Yeast Kinesin-5 Motor Protein CIN8 Promotes Accurate Chromosome Segregation
title_full_unstemmed Yeast Kinesin-5 Motor Protein CIN8 Promotes Accurate Chromosome Segregation
title_short Yeast Kinesin-5 Motor Protein CIN8 Promotes Accurate Chromosome Segregation
title_sort yeast kinesin-5 motor protein cin8 promotes accurate chromosome segregation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316075/
https://www.ncbi.nlm.nih.gov/pubmed/35883587
http://dx.doi.org/10.3390/cells11142144
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