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Title: Studies on the interplay between the microtubule cytoskeleton and Cdc2-cyclin B kinase at the onset of mitosis in fission yeast
Author: Renwick, Steven John
ISNI:       0000 0001 3514 1581
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2005
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The aim of the work presented in this thesis was to investigate the roles of the microtubule cytoskeleton in the S. pombe cell cycle. I initially confirmed a previous observation by Hyams and colleagues that destruction of the microtubule cytoskeleton with the microtubule destabilising drug thiabendazole, inhibits Cdc2 kinase activation at the G2 to mitosis transition (Alfa et al., 1990). Importantly, this delay was not due to activation of the DNA damage or spindle assembly checkpoints and thus may represent a new pathway. Further investigation revealed that microtubule destruction also affected the re-localisation of the Cdc2 mitotic cyclin binding partner Cdcl3 to the spindle pole bodies at the onset of mitosis, giving rise to a possible explanation for the inhibition of Cdc2 activity. To investigate further the role of Cdcl3 in the mitotic response to microtubule damage I characterised the thiabendazole sensitivity of a cdc!3-l 17 strain bearing a temperature sensitive mutant in Cdcl3 (Booher and Beach, 1988). I found that cdclS- 117 cells were defective in the accuracy of chromosome segregation and performed a genetic screen for multicopy suppressors of the sensitivity of cdc!3-117 to thiabendazole. I identified several suppressors including a truncated allele of a gene encoding a protein with homology to the S. cerevisiae Daml microtubule binding protein that has a role in establishing chromosome bi-orientation (Cheeseman et al., 2002). Localisation studies established that Daml binds to the interface between mitotic spindle microtubules and kinetochores only in mitosis. To investigate the role of Daml in mitosis, the daml gene was deleted. Cells lacking Daml showed frequent mitotic abnormalities and a high rate of chromosome mis-segregation. Initial studies suggest that Daml is a member of a 10 sub-unit complex that includes Duol, Dadl, Spc34, and Askl.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available