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Title: Molecular analysis of chromosome movement by microtubule depolymerisation-coupled pulling
Author: Auckland, Philip
ISNI:       0000 0004 7431 6614
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2016
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QH301 Biology