Regulation of chromosome segregation by Shugoshin and protein phosphatase 2A in budding yeast
dc.contributor.advisor
Marston, Adele
en
dc.contributor.author
Clift, Dean
en
dc.date.accessioned
2011-01-19T16:18:09Z
dc.date.available
2011-01-19T16:18:09Z
dc.date.issued
2010
dc.description.abstract
The 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.identifier.uri
http://hdl.handle.net/1842/4672
dc.language.iso
en
dc.publisher
The University of Edinburgh
en
dc.relation.hasversion
Clift, 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.subject
shugoshin
en
dc.subject
PPZA
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dc.subject
separase
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dc.subject
chromosome segregaton
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dc.title
Regulation of chromosome segregation by Shugoshin and protein phosphatase 2A in budding yeast
en
dc.type
Thesis or Dissertation
en
dc.type.qualificationlevel
Doctoral
en
dc.type.qualificationname
PhD Doctor of Philosophy
en
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