{"@context":"http://iiif.io/api/presentation/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/manifest.json","@type":"sc:Manifest","label":"Role of a metabolic burst and titration of an unstable activator in the entrainment of division to growth","metadata":[{"label":"dc.description.sponsorship","value":"This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree."},{"label":"dc.format","value":"Monograph"},{"label":"dc.format.medium","value":"Electronic Resource"},{"label":"dc.identifier.uri","value":"http://hdl.handle.net/11401/70956"},{"label":"dc.language.iso","value":"en_US"},{"label":"dc.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.abstract","value":"Most cells coordinate increase in mass with an increase in cell number. Using simu- lations I show that exponentially growing cells require size control (a molecular link between growth and division) to maintain a population with a biologically reasonable cell size distribution, though linearly growing cells do not. The main regulator of cell-cycle commitment in budding yeast is the G1 cyclin Cln3, which partners with the Cyclin Dependent Kinase (CDK) Cdc28 to activate the transcription factor SBF and promote transcription of over 150 genes involved in cell-cycle progression. Commitment to Start (passage from G1 into S) involves transition from a low Cyclin/CDK state to a high Cyclin/CDK state, and this transition is driven largely by Cln3/CDK activity. Cln3 is recruited indirectly to DNA by SBF where it both activates transcriptional activators and inhibits transcriptional repressors. Cln3 is unstable, so the amount of Cln3 in cells is proportional to their size (biosynthetic capacity). By measuring cell volume throughout the cell-cycle we show that addition of more SBF binding sites increases cell size, and that this increase varies depending on the genetic dose of CLN3. This suggests that cells may measure size by titrating an unknown and noisy amount of Cln3 protein to a known and constant number of SBF binding sites. Slowly growing cells produce less cyclinprotein per unit mRNA than do rapidly growing cells. Using a genetic system in which I can tightly control the level of cyclin expression I show that slowly growing cells require less cyclin expression to pass through Start; this growth dependent threshold requirement may be a result of the instability of Cln3. Finally, I show that in addition to the transcrip- tional positive feedback loop that switches cells from low Cln/CDK to high Cln/CDK, there may be contribution from a metabolic feedback loop in which Cyclin/CDK activity may drive, and be driven by, metabolic changes during Start. These metabolic changes involve the sudden conversion of stored carbohydrate (glycogen and trehalose) to glucose in late G1 phase. I show that carbohydrate mutants have cell-size phenotypes, that genes involved in carbohydrate metabolism are CDK targets and that genes involved in cell- cycle control are Protein Kinase A (PKA) targets. I show that there is a spike in PKA activity around Start, and that the transcriptional profile around Start in ethanol grown cells is similar to that of ethanol grown cells spiked with glucose. These results suggest that slowly growing carbon-deprived cells briefly become rapidly growing carbon-rich cells around Start, and this increase in biosynthetic capacity may drive cells through Start."},{"label":"dcterms.available","value":"2012-05-15T18:02:25Z"},{"label":"dcterms.contributor","value":"Aaron Neimann"},{"label":"dcterms.creator","value":"Carey, Lucas Buckler"},{"label":"dcterms.dateAccepted","value":"2015-04-24T14:45:17Z"},{"label":"dcterms.dateSubmitted","value":"2015-04-24T14:45:17Z"},{"label":"dcterms.description","value":"Department of Genetics"},{"label":"dcterms.format","value":"Application/PDF"},{"label":"dcterms.identifier","value":"Carey_grad.sunysb_0771E_10015.pdf"},{"label":"dcterms.issued","value":"2010-05-01"},{"label":"dcterms.language","value":"en_US"},{"label":"dcterms.provenance","value":"Made available in DSpace on 2015-04-24T14:45:17Z (GMT). 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