The assembly of a bipolar spindle lies at the heart of mitotic chromosome segregation. In animal somatic cells, the process of spindle assembly involves multiple complex interactions between various cellular compartments, including an emerging antiparallel microtubule network, microtubule-associated motor proteins and spindle assembly factors, the cell's cortex, and the chromosomes themselves. The result is a dynamic structure capable of aligning pairs of sister chromatids, sensing chromosome misalignment, and generating force to segregate the replicated genome into two daughters. Because the centrosome lies at the center of the array of microtubule minus-ends, and the essential one-to-two duplication of the centrosome prior to mitosis is linked to cell cycle progression, this organelle has long been implicated as a device to generate spindle bipolarity. However, this classic model for spindle assembly is challenged by observations and experimental manipulations demonstrating that acentrosomal cells can and do form bipolar spindles, both mitotic and meiotic. Indeed, recent comprehensive proteomic analysis of centrosome-dependent versus independent mitotic spindle assembly mechanisms reveals a large, common set of genes required for both processes, with very few genes needed to differentiate between the two. While these studies cast doubt on an absolute role for the centrosome in establishing spindle polarity, it is clear that having too few or too many centrosomes results in abnormal chromosome segregation and aneuploidy. Here we review the case both for and against the role of the centrioles and centrosomes in ensuring proper assembly of a bipolar spindle, an essential element in the maintenance of genomic stability.
|Original language||English (US)|
|Title of host publication||International Review of Cell and Molecular Biology|
|Number of pages||39|
|State||Published - 2014|
|Name||International Review of Cell and Molecular Biology|
Bibliographical noteFunding Information:
I apologize to those whose work was not cited, due to space limitations. I would like to thank Dr Liz Collins, Dr Tom Durcan, and Dr Jess Hornick for their excellent contributions to centrosome biology, and for generating many outstanding microscopic images over the years (some of which are included here). Studies in the author's lab are supported by the US DOD CDMRP (CA130436), the Austin, MN “Paint the Town Pink” fund, and the Hormel Foundation.
- Cell cycle progression
- Chromosome segregation
- Mitotic spindle assembly
- Spindle bipolarity