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Terry Orr-Weaver. Pesin, Jillian Annice (Pesin-Fulop) Massachusetts Institute of Technology. Dept. of Biology. Massachusetts Institute of Technology. Department of Biology 2008-09-03T15:32:47Z 2008-09-03T15:32:47Z 2007 2008 http://hdl.handle.net/1721.1/42399 237101025 Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, February 2008. Includes bibliographical references. Meiosis is a modified cell cycle in which two round of chromosome segregation occur without an intervening DNA synthesis phase. As in mitosis, these cell divisions are driven in part by proteolysis mediated by the Anaphase-Promoting Complex/ Cyclosome (APC/C). During oogenesis of multicellular organisms, molecular control of meiosis has an added complexity because these divisions must be coordinated with the growth and development of the oocyte as well as its fertilization. The Drosophila gene cortex (cort), a putative female meiosis-specific APC/C activator, provides a unique opportunity to study the role of the APC/C in metazoan meiosis. We demonstrate that CORT protein associates with the core APC/C in ovaries, confirming its function as an activator of the APC/C. CORT triggers the sequential degradation of mitotic Cyclins in meiosis, as well as causing the degradation of PIMPLES, the Drosophila homolog of Securin. Both post-transcriptional and post-translational regulation of cort result in expression of CORT protein being restricted to the meiotic divisions. Cytoplasmic polyadenylation of cort mRNA is tightly correlated with appearance of the protein in mature oocytes. At the end of meiosis, CORT is rapidly degraded in an APC/C and D-box-dependent manner. We initiated a genetic screen to identify substrates of APC/CCORT using grauzone (grau) mutants, a gene encoding a transcriptional activator of cort. We have identified at least one deficiency on the third chromosome, Df(3R)p-XT103, that dominantly suppresses grau. Levels of BEL, a protein encoded within this deficiency, are elevated in cort mutants. Our analysis of the regulation of CORT protein levels reveals one mechanism that may be important for developmental control of meiotic progression and the transition from meiosis to embryonic mitotic divisions. In addition, our screen to identify meiosisspecific substrates of APC/CCORT has the potential to uncover novel regulators of meiosis in a multicellular organism. by Jillian Annice Pesin. Ph.D. 198 leaves eng Massachusetts Institute of Technology M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 Biology. The developmental role and regulation of the Anaphase-Promoting Complex/Cyclosome in Drosophila meiosis Thesis application/pdf Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="536919d4-3be9-4374-935a-9c4989b834a1"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Language>eng</Language> <Title>The developmental role and regulation of the Anaphase-Promoting Complex/Cyclosome in Drosophila meiosis</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2008</PublicationDate> <Authors> <Author> <DisplayName>Pesin, Jillian Annice (Pesin-Fulop)</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>http://dspace.mit.edu/handle/1721.1/7582</License> <Keyword>Biology.</Keyword> <Abstract>Meiosis is a modified cell cycle in which two round of chromosome segregation occur without an intervening DNA synthesis phase. As in mitosis, these cell divisions are driven in part by proteolysis mediated by the Anaphase-Promoting Complex/ Cyclosome (APC/C). During oogenesis of multicellular organisms, molecular control of meiosis has an added complexity because these divisions must be coordinated with the growth and development of the oocyte as well as its fertilization. The Drosophila gene cortex (cort), a putative female meiosis-specific APC/C activator, provides a unique opportunity to study the role of the APC/C in metazoan meiosis. We demonstrate that CORT protein associates with the core APC/C in ovaries, confirming its function as an activator of the APC/C. CORT triggers the sequential degradation of mitotic Cyclins in meiosis, as well as causing the degradation of PIMPLES, the Drosophila homolog of Securin. Both post-transcriptional and post-translational regulation of cort result in expression of CORT protein being restricted to the meiotic divisions. Cytoplasmic polyadenylation of cort mRNA is tightly correlated with appearance of the protein in mature oocytes. At the end of meiosis, CORT is rapidly degraded in an APC/C and D-box-dependent manner. We initiated a genetic screen to identify substrates of APC/CCORT using grauzone (grau) mutants, a gene encoding a transcriptional activator of cort. We have identified at least one deficiency on the third chromosome, Df(3R)p-XT103, that dominantly suppresses grau. Levels of BEL, a protein encoded within this deficiency, are elevated in cort mutants. Our analysis of the regulation of CORT protein levels reveals one mechanism that may be important for developmental control of meiotic progression and the transition from meiosis to embryonic mitotic divisions. In addition, our screen to identify meiosisspecific substrates of APC/CCORT has the potential to uncover novel regulators of meiosis in a multicellular organism.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>