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dc.contributor.advisorMarston, Adele
dc.contributor.authorClift, Dean
dc.date.accessioned2011-01-19T16:18:09Z
dc.date.available2011-01-19T16:18:09Z
dc.date.issued2010
dc.identifier.urihttp://hdl.handle.net/1842/4672
dc.description.abstractThe accurate distribution of genetic information (chromosomes) during cell division is essential for the growth and proliferation of all living organisms. Errors in chromosome segregation in humans have been linked to cancer progression, infertility and developmental diseases. In my PhD I study how chromosome segregation is regulated in the genetically amenable budding yeast Saccharomyces cerevisiae. Since the mechanisms of chromosome segregation are highly conserved amongst eukaryotes, studies in yeast will provide a fundamental understanding of this process. Sgo1 is the budding yeast member of a highly conserved family of shugoshin proteins, which play a key role in chromosome segregation. My work characterizes a previously unidentified role of Sgo1 in inhibiting separase; an enzyme that triggers chromosome segregation by cleaving the cohesin protein complex that holds replicated chromosomes together. I demonstrate that this novel function of Sgo1 requires a specific form of Protein Phosphatase 2A (PP2ACdc55), an enzyme that itself is highly conserved amongst eukaryotes. I propose that PP2ACdc55 is a separase inhibitor that is employed by Sgo1 when sister chromatids are not under tension. Finally, I go on to initiate preliminary studies into the mechanism whereby PP2ACdc55 inhibits separase. In sum, this study uncovers an additional layer of separase regulation mediated by Sgo1 and PP2ACdc55 and therefore makes a significant contribution to our understanding of the all-or-nothing nature of chromosome segregation.en
dc.language.isoenen
dc.publisherThe University of Edinburghen
dc.relation.hasversionClift, D., F. Bizzari and A. L. Marston. 2009. Shugoshin prevents cohesin cleavage by PP2A(Cdc55)-dependent inhibition of separase. Genes Dev 23: 766-80.en
dc.subjectshugoshinen
dc.subjectPPZAen
dc.subjectseparaseen
dc.subjectchromosome segregatonen
dc.titleRegulation of chromosome segregation by Shugoshin and protein phosphatase 2A in budding yeasten
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen


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