Centrosome separation; a careful balancing act

Abstract

Centrosome separation is critical for formation of a bipolar spindle and the subsequent accurate segregation of chromosomes during mammalian cell mitosis. The multiple mechanisms that regulate this important process are still being elucidated, with separate pathways acting before nuclear envelope breakdown (NEBD) in prophase and post-NEBD in prometaphase. These mechanisms include cortical actin dynamics, multiple molecular motors and microtubule (MT) pushing forces from kinetochores. However, the plus-end-directed kinesin Eg5 is irrefutably the most important player identified so far. The MT-sliding activity of Eg5 is essential for centrosome separation in prometaphase across many species,1 and also plays a role in the less-understood prophase pathway in mammalian cells.2 Treatment of cells with Eg5 inhibitors leads to monopolar spindles and mitotic arrest,3 which has led to much interest in these drugs as potential anti-cancer therapies over the last few years.