Vardy, Leah Karen Anne;
(2001)
The role of fission yeast γ-tubulin interacting proteins in mitosis.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
alp4+ and alp6+ were isolated as temperature sensitive morphology mutants in fission yeast. They encode the homologues of the human γ-tubulin interacting proteins H.s. GCP2 and H.s. GCP3. Both proteins localise to the Spindle Pole Body (SPB) and show both genetic and biochemical interactions with each other and γ-tubulin. They exist in a large γ-tubulin complex that is comparable in size to that found in mammalian cells. Temperature sensitive mutants of these genes show abnormalities in cytoplasmic and spindle microtubules at the restrictive temperature. Alp4 plays an essential role in G1 phase for progression through the following mitosis. If this period is passed at the restrictive temperature cells fail to form bipolar spindles resulting in abnormal chromosome segregation as mitosis progresses. The alp4 mutant retains the γ-tubulin complex but fails in its recruitment to the SPB. The Mad2 checkpoint is activated in alp4ts at 36°C in response to the monopolar spindles. These cells, however, fail to arrest fully and proceed with septation. This suggests that the γ-tubulin complex plays a role in the prevention of septation in Mad2 arrested cells. alp16+ was cloned as a multicopy suppressor of alp6ts and shows genetic and biochemical interactions with γ-tubulin. alp4ts, alp6ts and alp16Δ are all checkpoint defective and cells fail to arrest in response to microtubule destabilising drugs at the permissive temperature. The data presented suggests that these proteins act in a Mad2 independent checkpoint pathway to arrest mitosis in response to TBZ. This thesis reports on the work done to characterise these mutants and determine the function of the proteins. Finally, the cloning and characterisation of a novel protein, Alp7, is described. Alp7 is a non-essential microtubule binding protein that plays a role in the regulation and progression of mitosis.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | The role of fission yeast γ-tubulin interacting proteins in mitosis |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest. |
| Keywords: | Biological sciences; Tubulin |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10102968 |
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