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DROSOPHILA MELANOGASTER DIS3 IS A DYNAMIC ENDO- AND 3’ to 5’ EXORIBONUCLEASE

Mamolen, Megan Christine
http://rave.ohiolink.edu/etdc/view?acc_num=case1278525341

Abstract Details

2010, Doctor of Philosophy, Case Western Reserve University, Molecular Biology and Microbiology.
Dis3 is an evolutionarily conserved and essential enzyme with functions in mitosis, and RNA processing and turnover. In this work, we employed both in vitro and in vivo techniques to examine the biochemical and cell biological characteristics of a metazoan Dis3 homolog. Here, for the first time, we show that Drosophila melanogaster Dis3 (dDis3) has in vitro exo- and endoribonuclease activities. Our results suggest that both activities employ metal-ion catalysis. Further, neither activity is substrate-specific in vitro. Interestingly, even though the exoribonuclease active site resides in the C-terminus, both activities require the presence of N-terminal Dis3 domains. We show that N-terminal domains mediate additional Drosophila Dis3 functions. For example, the Drosophila Dis3 N-terminus affects nuclear localization. The dDis3 N-terminus also contains a mitochondrial targeting sequence. Finally, N-terminal domains are responsible for interactions with exosome proteins and the nuclear import factor Importin-α3. This study demonstrates that Drosophila melanogaster Dis3 is a complex enzyme with multiple ribonuclease activities, localization patterns, and protein-protein interactions.
Erik Andrulis, PhD (Advisor)
Jonathan Karn, PhD (Committee Chair)
Alan Tartakoff, PhD (Committee Member)
Peter Harte, PhD (Committee Member)
182 p.
Biochemistry; Biology; Cellular Biology; Experiments; Molecular Biology; Scientific Imaging
Dis3; exosome; endoribonuclease; exoribonuclease; mitochondria; RNA turnover

Recommended Citations

Citations

  • Mamolen, M. C. (2010). DROSOPHILA MELANOGASTER DIS3 IS A DYNAMIC ENDO- AND 3’ to 5’ EXORIBONUCLEASE [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1278525341

    APA Style (7th edition)

  • Mamolen, Megan. DROSOPHILA MELANOGASTER DIS3 IS A DYNAMIC ENDO- AND 3’ to 5’ EXORIBONUCLEASE. 2010. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1278525341.

    MLA Style (8th edition)

  • Mamolen, Megan. "DROSOPHILA MELANOGASTER DIS3 IS A DYNAMIC ENDO- AND 3’ to 5’ EXORIBONUCLEASE." Doctoral dissertation, Case Western Reserve University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1278525341

    Chicago Manual of Style (17th edition)

case1278525341
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© 2010, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.