Regulation of microtubule dynamics and distribution by MCAK during mitosis
by Rizk, Rania S., Ph.D., INDIANA UNIVERSITY, 2009, 234 pages; 3380125

Abstract:

Cell division is a complex biological process that is essential for the normal development of an organism. Cell division is carried out by the mitotic spindle, which is the cellular machine that is utilized to insure equal chromosome segregation into the two daughter cells. The spindle is composed of dynamic microtubules (MTs) and associated proteins that drive spindle assembly, chromosome alignment, and chromosome segregation. MTs are inherently dynamic polymers that exhibit a property called dynamic instability, wherein a population of MTs alternate randomly between phases of growth and shrinkage. While purified MTs undergo dynamic instability, MTs in cells are several-fold more dynamic than those in vitro, highlighting the importance of proteins that regulate MT dynamics. MT dynamics are also highly regulated in cells. At the onset of mitosis, there is a dramatic increase in MT dynamics to allow for the assembly of the mitotic spindle. Within the spindle itself, there are at least three different subclasses of MTs, each having distinct functions and dynamic properties. While it is clear that changes in MT dynamics are required for proper cell cycle progression and spindle assembly, it remains unclear how individual cellular factors contribute to the regulation of MT dynamics within the spindle. An important MT dynamics regulator is the kinesin-related protein MCAK, which is needed for proper mitotic spindle assembly. To examine how cells manage their MT polymer and how MCAK contributes to this process, I perturbed MCAK function and then examined the changes in mitotic spindle organization and dynamics using high-resolution microscopy. My work established that MCAK differentially affects MT polymer organization and dynamics within the spindle, and that these dynamics are most crucial upon mitotic entry. This work has provided a deeper understanding of the molecular mechanisms underlying the regulation of MT dynamics throughout mitosis.

 
AdviserClaire E. Walczak
SchoolINDIANA UNIVERSITY
SourceDAI/B 70-12, p. , Dec 2009
Source TypeDissertation
SubjectsMolecular biology; Cellular biology
Publication Number3380125
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