When a cell divides, it must segregate all of its chromosomes equally into two daughter cells, and concomitantly segregate cytoplasmic cell fate determinants through cytokinesis. Both chromosome segregation and cytokinesis are coordinated by the mitotic spindle, a microtubule network constructed and disassembled at every cell division. A large number of proteins modulate microtubule nucleation, dynamics, and interactions in order to assemble and position the spindle, align and segregate chromosomes, and coordinate interactions between the ends of microtubules and the cell cortex. For most cells, even the slightest uncorrected error in spindle function can lead to defective segregation of chromosomes or cell fate determinants, often leading to eventual cell death, or worse, activation of oncogenes or loss of tumor suppressors, which may facilitate the path towards cancer. A major focus of the lab is in uncovering the mechanisms and regulatory pathways that guide the formation and function of the mitotic spindle to ensure genome stability.
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Mechanisms of Mitotic Spindle Assembly and Chromosome Segregation
Anaphase cell. Green: TPX2.
Red: kinetochores, Blue: DNA
TPX2 regulates spindle elongation after nuclear envelope breakdown