Mitosis is the process by which new cells are formed. Following accurate duplication of chromosomes, a cell must segregate its chromosomes into separate daughter cells with great accuracy. Failure to do so can result in genomic instability. Thus, entry into mitosis is tightly regulated via complex protein interactions. Microtubules (MTs) are versatile Tubulin polymers that constitute a considerable portion of the cytoskeleton, and it is the dramatic rearrangement of MTs upon mitotic entry that is required to build the mitotic spindle – the structure responsible for segregating the duplicated sister chromatids. MTs are modulated by MT-Associated Proteins (MAPs) that enact major MT rearrangements during mitosis. Identifying and understanding the role of MAPs is essential to the study of MT behaviour during mitosis. Recently, an RNAi screen for Drosophila MAPs identified two proteins that are the subject of this thesis; Msd1 and dTD-60. This thesis demonstrates that Msd1 is a novel MAP that is a component of the recently identified Augmin complex – the action of which is to generate a novel and redundant population of MTs within the mitotic spindle from existing MTs. Experiments described below demonstrate that Msd1 is required for Augmin-directed MT generation, and further investigate the role of this novel population of MTs within the developing fruit fly. Furthermore, a role for Msd1 in central spindle formation during anaphase in Drosophila is identified. dTD-60, the Drosophila homologue of human TD-60 (hTD-60), is the subject of another study described in this thesis. While hTD-60 has a role in metaphase progression through interaction with the Chromosomal Passenger Complex, a contrasting role for dTD-60 is investigated here. This thesis describes both a divergent localisation and phenotype of dTD-60, and further investigates the role of dTD-60 and its interactors in mitotic spindle formation.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:580870 |
| Date | January 2011 |
| Creators | Duncan, Tommy |
| Contributors | James, Wakefield |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://ora.ox.ac.uk/objects/uuid:3ed4021f-2ccc-4821-b7c5-40b06d5639b7 |
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