Article abstract
Nature Cell Biology 11, 27 - 35 (2008)
Published online: 7 December 2008 | doi:10.1038/ncb1809
Genome stability is ensured by temporal control of kinetochore–microtubule dynamics
Samuel F. Bakhoum1, Sarah L. Thompson1, Amity L. Manning1 & Duane A. Compton1
Abstract
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.
- Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755; Norris Cotton Cancer Center, Lebanon, NH 03766, USA.
Correspondence to: Duane A. Compton1 e-mail: duane.a.compton@dartmouth.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Correcting SYNful attachmentsNature Cell Biology News and Views (01 Mar 2004)
Chromosomes walk the lineNature Cell Biology News and Views (01 Apr 2006)
RESEARCH
Aurora controls sister kinetochore mono-orientation and homolog bi-orientation in meiosis-IThe EMBO Journal Article (31 Oct 2007)
The DASH complex and Klp5/Klp6 kinesin coordinate bipolar chromosome attachment in fission yeastThe EMBO Journal Article (17 Aug 2005)
See all 59 matches for Research
