Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.598272
Title: Mechanisms regulating eukaryotic mitosis
Author: Daniels, M. J.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2005
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Abstract:
The fertilised egg gives rise to the entire organism through the coordination of high fidelity chromosome replication and then segregation. When this mechanism is corrupted cells acquire stable genetic mutations that absolve them from the normal proliferative impediments at work to keep the organism healthy. This is the basis of cancer. In order to understand and then rationally treat cancer we must understand the process of cell division. In this thesis I elucidate novel information pertaining to three mechanisms that guide a cell through the process of mitosis. Firstly as cells enter mitosis I have identified the requirement of the Promyelocytic Leukaemia (PML) tumour suppressor for the integrity of the antephase checkpoint. PML limits the intracellular distribution and mobility of the CHFR checkpoint protein previously known to be required for the antephase checkpoint. During mitotic progression the RanGTPase orchestrates several distinct events. By showing that the principle GTPase activating protein (RanGAP1) is the subject of multiple mitotic phosphorylations that regulate its activity I have identified part of the mechanism that allows the cell cycle to control the actions of the RanGTPase in mitosis. Finally I have provided evidence that the tumour suppressor BRCA2 is required during the process of cytokinesis, and that in its absence cells frequently become aneuploid. Thus I have identified a new route of genetic instability in a hereditary form of cancer.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.598272  DOI: Not available
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