Auckland, Philip (2016) Molecular analysis of chromosome movement by microtubule depolymerisation-coupled pulling. PhD thesis, University of Warwick.

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Abstract

The alignment of all chromosomes at the spindle equator is a universal feature of mitosis in metazoans. Kinetochores mediate this migratory event by either sliding chromosomes along the lattice of spindle microtubules (lateral sliding) or by coupling them to depolymerising microtubule plus-ends (depolymerisation-coupled pulling, DCP). While a robust molecular description of the lateral sliding mechanism has been generated both in vivo and in vitro over the past decade, similar models of DCP are lacking. This may represent the comparable complexity of DCP, where multiple redundant kinetochore factors contribute to specific DCP sub-steps that together enable congression. Moreover, unlike the lateral sliding motor CENP-E, many candidate DCP factors have pleiotropic roles in the kinetochore and convincingly separating these in vivo is complex. Here, we discuss how combining high-resolution kinetochore tracking with specific molecular perturbations enables the assignment of distinct DCP functions to kinetochore components. This enables us to build an integrated model of chromosome congression in vivo, which acts downstream of the well established microtubule attachment machinery. We also resolve some of the previously reported discrepancies associated with depletion of kinetochore proteins. Finally, this work identifies a previously overlooked step in wild-type congression.

Item Type:	Thesis or Dissertation (PhD)
Subjects:	Q Science > QH Natural history > QH301 Biology
Library of Congress Subject Headings (LCSH):	Mitosis, Spindle (Cell division), Chromosomes -- Analysis, Microtubules
Official Date:	October 2016
Dates:	Date Event October 2016 Submitted
Institution:	University of Warwick
Theses Department:	Warwick Medical School
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	McAinsh, Andrew D.
Format of File:	pdf
Extent:	192 leaves : illustrations, charts
Language:	eng

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