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You searched for +publisher:"Vanderbilt University" +contributor:("Dr. Tony Weil"). Showing records 1 – 2 of 2 total matches.

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Vanderbilt University

1. McCann, Tyler Scott. Elucidation of the Biological Function of the RPC Family Ubiquitin Ligase Asr1.

Degree: PhD, Cell and Developmental Biology, 2016, Vanderbilt University

Proper regulation of gene transcription is an essential process for any cell. Failure to precisely control the procedure of transcription can lead to developmental defects, disease, and even death. Within the last 20 years, ubiquitin, and other factors of the ubiquitin proteasome system have been shown to be extensively involved in the control of various steps of transcription. The Saccharomyces cerevisiae protein Asr1, is the defining member of an evolutionarily conserved set of proteins that contain a RING finger, a PHD finger, and a domain that binds the C-terminal repeat region of RNA polymerase II (RNAPII) called the RPC protein family. Asr1 is recruited to RNAPII in response to hyperphosphorylation of its regulatory C-terminal tail. Once bound, Asr1 oligoubiquitylates at least two subunits of RNAPII, leading to the ejection of the dissociable heterodimer Rpb4 and Rpb7, as well as the transcriptional inactivation of the polymerase complex. Despite the clear biochemical effects Asr1 has on RNAPII, a biological role for Asr1 within the cell has remained elusive. Within this dissertation, I present evidence that Asr1 is involved in the silencing of transcription of genes located at subtelomeric regions. Asr1 has been observed to associate with subtelomeric chromatin, and disruption of the ability of Asr1 to ubiquitylate RNAPII induces transcription at these regions. Asr1 also physically associates with Ubp3, a ubiquitin specific protease with a known role in the regulation of silent chromatin at sub-telomeric regions. I show that Asr1 and Ubp3 have antagonistic roles in both the ubiquitylation of RNAPII as well as the transcription of genes located in telomere proximal regions. The evidence presented in this dissertation reveal the importance of non-proteolytic ubiquitylation in the control of transcription, but also sheds light on a poorly understood family of eukaryotic ubiquitin-ligases. Advisors/Committee Members: Dr. Todd Graham (committee member), Dr. Melanie Ohi (committee member), Dr. Tony Weil (committee member), Dr. Stephen Hann (Committee Chair).

Subjects/Keywords: ubiquitin; silencing; RNA polymerase II; transcription; chromatin

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

McCann, T. S. (2016). Elucidation of the Biological Function of the RPC Family Ubiquitin Ligase Asr1. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/10415

Chicago Manual of Style (16th Edition):

McCann, Tyler Scott. “Elucidation of the Biological Function of the RPC Family Ubiquitin Ligase Asr1.” 2016. Doctoral Dissertation, Vanderbilt University. Accessed October 01, 2020. http://hdl.handle.net/1803/10415.

MLA Handbook (7th Edition):

McCann, Tyler Scott. “Elucidation of the Biological Function of the RPC Family Ubiquitin Ligase Asr1.” 2016. Web. 01 Oct 2020.

Vancouver:

McCann TS. Elucidation of the Biological Function of the RPC Family Ubiquitin Ligase Asr1. [Internet] [Doctoral dissertation]. Vanderbilt University; 2016. [cited 2020 Oct 01]. Available from: http://hdl.handle.net/1803/10415.

Council of Science Editors:

McCann TS. Elucidation of the Biological Function of the RPC Family Ubiquitin Ligase Asr1. [Doctoral Dissertation]. Vanderbilt University; 2016. Available from: http://hdl.handle.net/1803/10415


Vanderbilt University

2. Neill, Meaghan Anne. Nitrogen Metabolism: Enzyme Expression and Protein Interactions in the Urea and Nitric Oxide Cycles.

Degree: PhD, Human Genetics, 2010, Vanderbilt University

The urea cycle enzymes play an important role in the processing of nitrogen to urea and in producing endogenous nitric oxide by the citrulline-nitric oxide cycle. This project characterizes the expression of urea and nitric oxide cycle enzymes and their intermediates at a cellular level. First, the expression of these enzymes in human tissues is examined. These findings reflect the expression of these genes in the human body at a baseline level. Second, the expression of these enzymes is determined in mouse tissue as well as concentrations of their intermediates (arginine and citrulline) and the end product nitric oxide. Here we discovered that citrulline is correlated with the production of nitric oxide metabolites in mouse tissues. Our third aim involved studying these enzymes in a cell culture environment and exposed to stimuli to measure changes in mRNA expression, protein expression and changes in the concentration of pathway intermediates (arginine and citrulline) as well as the end product nitric oxide. Finally, we examined protein interactions involved in the nitric oxide and urea cycle enzymes. This work highlights the functional co-localization and interactions of the components and intermediates of the urea and nitric oxide cycles, which has important implications for understanding the molecular biology underlying diseases associated with nitric oxide and urea cycle dysfunction. Advisors/Committee Members: Dr. Marshall Summar (committee member), Dr. Doug Mortlock (committee member), Dr. Tony Weil (committee member), Dr. Michael Aschner (committee member), Dr. Deborah Murdock (Committee Chair).

Subjects/Keywords: mRNA expression; protein interactions; nitric oxide cycle; urea cycle; protein expression; nitrogen metabolism

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Neill, M. A. (2010). Nitrogen Metabolism: Enzyme Expression and Protein Interactions in the Urea and Nitric Oxide Cycles. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/11764

Chicago Manual of Style (16th Edition):

Neill, Meaghan Anne. “Nitrogen Metabolism: Enzyme Expression and Protein Interactions in the Urea and Nitric Oxide Cycles.” 2010. Doctoral Dissertation, Vanderbilt University. Accessed October 01, 2020. http://hdl.handle.net/1803/11764.

MLA Handbook (7th Edition):

Neill, Meaghan Anne. “Nitrogen Metabolism: Enzyme Expression and Protein Interactions in the Urea and Nitric Oxide Cycles.” 2010. Web. 01 Oct 2020.

Vancouver:

Neill MA. Nitrogen Metabolism: Enzyme Expression and Protein Interactions in the Urea and Nitric Oxide Cycles. [Internet] [Doctoral dissertation]. Vanderbilt University; 2010. [cited 2020 Oct 01]. Available from: http://hdl.handle.net/1803/11764.

Council of Science Editors:

Neill MA. Nitrogen Metabolism: Enzyme Expression and Protein Interactions in the Urea and Nitric Oxide Cycles. [Doctoral Dissertation]. Vanderbilt University; 2010. Available from: http://hdl.handle.net/1803/11764

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