Regulation of microtubule stability in Saccharomyces cerevisiae
Item
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Title
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Regulation of microtubule stability in Saccharomyces cerevisiae
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Identifier
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d_2009_2013:e917044d0d54:10790
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identifier
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11104
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Creator
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Shohat, Aya,
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Contributor
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Dan Eshel
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Date
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2011
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Language
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English
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Publisher
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City University of New York.
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Subject
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Molecular biology | Cellular biology | Microtubules | Mitotic Spindle | Motor proteins
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Abstract
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The integrity of chromosome segregation during mitosis is essential for the propagation of genetic information to daughter cells during cell division. In yeast, it is achieved in four microtubule-dependent steps: first is spindle assembly, which involves the migration of duplicated microtubule organizing centers to form a bipolar spindle by prophase; second is orientation of the mitotic spindle at the site of cytokinesis; third- chromosome movement along kinetochore microtubules (anaphase A); and fourth, complete chromosome segregation through spindle elongation through interpolar microtubules (anaphase B). Signaling pathways have been implicated in the regulation of microtubule dynamics and stability, which is required for these processes. This work identifies additional protein regulators of microtubule stability using mutants of key mitotic motor proteins, specifically, Cin8p, Kip1p, and Dyn1p. Loss of Cin8p function in the absence of either Kip1p or Dyn1p is lethal. Haploid cells that carry the cin8-3 temperature sensitive allele in a deletion background of either KIP1 or DYN1 cannot grow above 35°C. Our studies suggest that suppressors of these mutant genotypes act by stabilizing microtubules. We propose that the mechanism of suppression involves enhancing signal-transduction cascades that regulate microtubule stability and dynamics. We found that FCP1 overexpression supressess the microtubule defect in our background and that this suppression requires the following genes to manifest: SWI6, SWI4, CLB2, ELM1, HSL1 and MRS6. These proteins, with a previously uncharacterized role in microtubule stability, may be candidate microtubule-associated proteins (MAPs) or novel regulators of MAPs (direct or indirect). In addition, a putative pathway to MT stability was drawn based on genetic interactions we established, epistatic experiments that were done and physical data we produced, combined with existing knowledge.
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Type
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dissertation
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Source
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2009_2013.csv
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degree
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Ph.D.
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Program
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Biology
