Genome stability is ensured by temporal control of kinetochore–microtubule dynamics

Samuel F. Bakhoum et al. 2008. Nature Cell Biology. 11, 27-35

Speaker: 高毓婷                                                         Time: 13:20~14:00, Apr. 15, 2009

Commentator: 張玲 老師                                          Place: Room 601

Abstract:

      Solid tumors are often highly aneuploid, and aneuploid cells are genetically unstable and whole chromosomes are frequently missegregated in a phenomenon called chromosomal instability (CIN). Chromosome segregation requires stable microtubule attachment at kinetochores, and those attachments must be dynamic to correct mal-orientations. Important regulators of microtubule dynamics during mitosis are the kinesin-13 proteins. Kinesin-13 proteins are non-motile and induce microtubule depolymerization by disassembling tubulin subunits from the polymer end. There are three distinct genes encoding, Kif2a, kif2b and MCAK/Kif2c three members. MCAK is the best-characterized member of the family and localizes to spindle poles, spindle midzone, and kinetochores. Cells utilize its microtubule depolymerase activity to destabilize inappropriate (merotelic) microtubule attachments at kinetochores. The other member, Kif2b, which is essential for spindle assembly, chromosome movement, and cytokinesis, localizes in kinetochores during early mitosis. Although MCAK and Kif2b are both important in the regulation of kinetochore-microtubule dynamics, their involvement in the regulation of microtubule attachment remains poorly understood. In this paper, the authors show that two microtubule-depolymerizing kinesins, Kif2b and MCAK, stimulate kinetochore- microtubule dynamics during distinct phases of mitosis to correct mal-orientations. In addition, stimulation of microtubule dynamics at kinetochores restores stability of chromosomally unstable tumor cells lines. Altogether, temporal control of microtubule attachment to chromosomes during mitosis plays a pivotal role in genome stability in human cells.

Reference:

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2.     S.L. Thompson, and D.A. Compton, Examining the link between chromosomal instability and aneuploidy in human cells. J Cell Biol 180 (2008) 665-72.