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Title: Roles for Mph1 kinase in the spindle checkpoint and chromosome segregation
Author: Milne, Laura
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2007
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The spindle checkpoint monitors the metaphase-to-anaphase transition to ensure accurate segregation of sister chromatids during mitosis to prevent aneuploidy. Mph1, the fission yeast homologue of Mps1 is one of the kinases involved in the spindle checkpoint. Deletion of Mph1 results in cells with a compromised spindle checkpoint. They do not arrest in response to spindle damage by drugs such as benomyl or mutations such as the cold sensitive tubulin mutant nda3. Instead they attempt to continue through anaphase with the result being cells showing cut phenotypes and ultimately cell death due to chromosome loss. Mph1 becomes phosphorylated during mitosis in an unperturbed mitosis and becomes hyperphosphorylated during spindle damage. The exact nature of this phosphorylation is unclear as no candidate kinase has been found that may be responsible for this modification, although autophosphorylation may play a role. In addition to a role of the spindle checkpoint Mph1, (as well as Bub1, another spindle checkpoint kinase), has a role in chromosome segregation. The Mph1 and Bub1 kinases appear to be the only spindle checkpoint components involved in chromosome segregation. In a deletion mutant a high percentage of lagging chromosomes and chromosome loss is observed, much the same as in a Bubl deletion. When a double deletion of Mphl and Bubl is made an additive effect is seen with respect to chromosome segregation. The percentage of lagging chromosomes and chromosome loss almost doubles with respect to the single mutants. This suggests that these two kinases have distinct target required for effective chromosome segregation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available