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    ANALYSIS OF THE AMINO-TERMINAL DOMAIN OF DROSOPHILA RBF1 INDICATES NOVEL ROLES IN CELL REGULATION

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    Author
    Ahlander, Joseph Andrew
    Issue Date
    2009
    Keywords
    DNA replication initiation
    origin recognition complex
    retinoblastoma tumor suppressor
    RNA processing
    Advisor
    Bosco, Giovanni
    Committee Chair
    Bosco, Giovanni
    
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    Show full item record
    Publisher
    The University of Arizona.
    Rights
    Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
    Abstract
    The retinoblastoma tumor suppressor protein (RB) is an important regulator of the cell cycle and development. Significantly, RB is inactivated in a majority of human cancers. Thus, elucidating the function of RB will give us a better understanding of how it prevents cancer. Many decades of research have yielded a detailed understanding of the role of RB in cell proliferation through transcriptional repression of target genes. However, the precise mechanisms of its action in many cellular pathways are poorly understood, including the control of DNA replication and post-transcriptional control of gene expression. Drosophila melanogaster presents a simplified genetic system to study cancer genes. Several published observations have suggested a role for RB in regulating DNA replication. Interestingly, other data indicate that RB associates with RNA processing factors. I have characterized novel protein-protein interactions with the Drosophila retinoblastoma tumor suppressor homologue Rbf, with an emphasis on its poorly characterized N-terminal domain. I describe the interaction of Rbf with the origin recognition complex, indicating a unique connection to DNA replication control. I also show that Rbf interacts with the RNA binding protein Squid, and review the literature that suggests potential role of RB/E2F in the control of RNA processing. The ability to control RNA processing may be an additional, unappreciated mode of gene regulation by RB. A focused study of the uncharacterized amino-terminal domain of Rbf has revealed new details about the retinoblastoma tumor suppressor in cell regulation, including DNA replication and RNA processing.
    Type
    text
    Electronic Dissertation
    Degree Name
    Ph.D.
    Degree Level
    doctoral
    Degree Program
    Molecular & Cellular Biology
    Graduate College
    Degree Grantor
    University of Arizona
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