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dc.contributor.advisorDannel McCollum, Ph.D.
dc.contributor.authorChoi, Sung Hugh
dc.date2022-08-11T08:08:42.000
dc.date.accessioned2022-08-23T16:04:57Z
dc.date.available2022-08-23T16:04:57Z
dc.date.issued2010-02-15
dc.date.submitted2010-03-31
dc.identifier.doi10.13028/s1dg-gz09
dc.identifier.urihttp://hdl.handle.net/20.500.14038/31783
dc.description.abstractThe proper transmission of genetic materials into progeny cells is crucial for maintenance of genetic integrity in eukaryotes and fundamental for reproduction of organisms. To achieve this goal, chromosomes must be attached to microtubules emanating from opposite poles in a bi-oriented manner at metaphase, and then should be separated equally through proper spindle elongation in anaphase. Failure to do so leads to aneuploidy, which is often associated with cancer. Despite the presence of a safety device called the spindle assembly checkpoint (SAC) to monitor chromosome bi-orientation, mammalian cells frequently possess merotelic kinetochore orientation, in which a single kinetochore binds microtubules emanating from both poles. Merotelically attached kinetochores escape from the surveillance mechanism of the SAC and when cells proceed to anaphase cause lagging chromosomes, which are a leading cause of aneuploidy in mammalian tissue cultured cells. The fission yeast monopolin complex functions in prevention of mal-orientation of kinetochores including merotelic attachments during mitosis. Despite the known importance of Cdk1 activity during mitosis, it has been unclear how oscillations in Cdk1 activity drive the dramatic changes in chromosome behavior and spindle dynamics that occur at the metaphase/anaphase transition. In two separate studies, we show how dynamic Cdk1 phosphorylation regulates chromosome segregation. First, we demonstrate that sequential phosphorylation and dephosphorylation of monopolin by Cdk1 and Cdc14 phosphatase respectively helps ensure the orderly execution of two discrete steps in mitosis, namely sister kinetochore bi-orientation at metaphase and spindle elongation in anaphase. Second, we show that elevated Cdk1 activity is crucial for correction of merotelic kinetochores produced in monopolin and heterochromatin mutants.
dc.language.isoen_US
dc.rightsCopyright is held by the author, with all rights reserved.
dc.subjectSchizosaccharomyces pombe Proteins
dc.subjectPhosphorylation
dc.subjectChromosome Segregation
dc.subjectMitotic Spindle Apparatus
dc.subjectCDC2 Protein Kinase
dc.subjectAnaphase
dc.subjectMetaphase
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBiochemical Phenomena, Metabolism, and Nutrition
dc.subjectEnzymes and Coenzymes
dc.subjectFungi
dc.titleThe Role of Dynamic Cdk1 Phosphorylation in Chromosome Segregation in Schizosaccharomyces pombe: A Dissertation
dc.typeDoctoral Dissertation
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1453&context=gsbs_diss&unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_diss/453
dc.legacy.embargo2011-03-12T00:00:00-08:00
dc.identifier.contextkey1255647
refterms.dateFOA2022-08-24T03:50:03Z
html.description.abstract<p>The proper transmission of genetic materials into progeny cells is crucial for maintenance of genetic integrity in eukaryotes and fundamental for reproduction of organisms. To achieve this goal, chromosomes must be attached to microtubules emanating from opposite poles in a bi-oriented manner at metaphase, and then should be separated equally through proper spindle elongation in anaphase. Failure to do so leads to aneuploidy, which is often associated with cancer. Despite the presence of a safety device called the spindle assembly checkpoint (SAC) to monitor chromosome bi-orientation, mammalian cells frequently possess merotelic kinetochore orientation, in which a single kinetochore binds microtubules emanating from both poles. Merotelically attached kinetochores escape from the surveillance mechanism of the SAC and when cells proceed to anaphase cause lagging chromosomes, which are a leading cause of aneuploidy in mammalian tissue cultured cells. The fission yeast monopolin complex functions in prevention of mal-orientation of kinetochores including merotelic attachments during mitosis. Despite the known importance of Cdk1 activity during mitosis, it has been unclear how oscillations in Cdk1 activity drive the dramatic changes in chromosome behavior and spindle dynamics that occur at the metaphase/anaphase transition. In two separate studies, we show how dynamic Cdk1 phosphorylation regulates chromosome segregation. First, we demonstrate that sequential phosphorylation and dephosphorylation of monopolin by Cdk1 and Cdc14 phosphatase respectively helps ensure the orderly execution of two discrete steps in mitosis, namely sister kinetochore bi-orientation at metaphase and spindle elongation in anaphase. Second, we show that elevated Cdk1 activity is crucial for correction of merotelic kinetochores produced in monopolin and heterochromatin mutants.</p>
dc.identifier.submissionpathgsbs_diss/453
dc.contributor.departmentBiochemistry and Molecular Pharmacology
dc.description.thesisprogramInterdisciplinary Graduate Program


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