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Reference - PMID:26031557 - Loss of kinesin-14 results in aneuploidy via kinesin-5-dependent microtubule protrusions leading to chromosome cut.

Reference summary

PubMed ID
PMID:26031557
Title
Loss of kinesin-14 results in aneuploidy via kinesin-5-dependent microtubule protrusions leading to chromosome cut.
Authors
Syrovatkina V, Tran PT
Citation
Nat Commun 2015 Jun 02;6:7322
Publication year
2015
Abstract
Aneuploidy-chromosome instability leading to incorrect chromosome number in dividing cells-can arise from defects in centrosome duplication, bipolar spindle formation, kinetochore-microtubule attachment, chromatid cohesion, mitotic checkpoint monitoring or cytokinesis. As most tumours show some degree of aneuploidy, mechanistic understanding of these pathways has been an intense area of research, to provide potential therapeutics. Here we present a mechanism for aneuploidy in fission yeast based on spindle pole microtubule defocusing by loss of kinesin-14 Pkl1, leading to kinesin-5 Cut7-dependent aberrant long spindle microtubule minus-end protrusions that push the properly segregated chromosomes to the site of cell division, resulting in chromosome cut at cytokinesis. Pkl1 localization and function at the spindle pole is mutually dependent on spindle pole-associated protein Msd1. This mechanism of aneuploidy bypasses the known spindle assembly checkpoint that monitors chromosome segregation.

Annotation

Multi-locus phenotype

FYPO:0001861 - increased minichromosome loss upon segregation during vegetative growth

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Genotypes:

FYPO:0003787 - long mitotic spindle microtubules protruding beyond spindle pole body

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FYPO:0000324 - mitotic metaphase/anaphase transition delay

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FYPO:0007969 - short-lived long mitotic spindle microtubules protruding beyond spindle pole body

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Single locus phenotype

FYPO:0007968 - cut with mitotic spindle microtubules protruding beyond spindle pole body

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Genotypes:

FYPO:0001861 - increased minichromosome loss upon segregation during vegetative growth

Genes:

Genotypes:

FYPO:0003787 - long mitotic spindle microtubules protruding beyond spindle pole body

Genes:

Genotypes:

FYPO:0000324 - mitotic metaphase/anaphase transition delay

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FYPO:0005709 - normal protein localization to mitotic spindle pole body during mitosis

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