<script type="text/javascript">
<!--
document.write('<div id="oa_widget"></div>');
document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=undefined&type=result"></script>');
-->
</script>
Most solid tumours are aneuploid and many frequently mis-segregate chromosomes. This chromosomal instability is commonly caused by persistent mal-oriented attachment of chromosomes to spindle microtubules. Chromosome segregation requires stable microtubule attachment at kinetochores, yet those attachments must be sufficiently dynamic to permit correction of mal-orientations. How this balance is achieved is unknown, and the permissible boundaries of attachment stability versus dynamics essential for genome stability remain poorly understood. Here we show that two microtubule-depolymerizing kinesins, Kif2b and MCAK, stimulate kinetochore-microtubule dynamics during distinct phases of mitosis to correct mal-orientations. Few-fold reductions in kinetochore-microtubule turnover, particularly in early mitosis, induce severe chromosome segregation defects. In addition, we show that stimulation of microtubule dynamics at kinetochores restores stability to chromosomally unstable tumour cell lines, establishing a causal relationship between deregulation of kinetochore-microtubule dynamics and chromosomal instability. Thus, temporal control of microtubule attachment to chromosomes during mitosis is central to genome stability in human cells.
Chromosome Aberrations, Recombinant Fusion Proteins, Green Fluorescent Proteins, Kinesins, Mitosis, Spindle Apparatus, Aneuploidy, Microtubules, Article, Genomic Instability, Cell Transformation, Neoplastic, Tubulin, Cell Line, Tumor, Chromosome Segregation, Humans, Kinetochores
Chromosome Aberrations, Recombinant Fusion Proteins, Green Fluorescent Proteins, Kinesins, Mitosis, Spindle Apparatus, Aneuploidy, Microtubules, Article, Genomic Instability, Cell Transformation, Neoplastic, Tubulin, Cell Line, Tumor, Chromosome Segregation, Humans, Kinetochores
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | 406 | |
popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network. | Top 1% | |
influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | Top 1% | |
impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network. | Top 1% |