In this dissertation I identify and define SWI/SNF, matrix-associated, actin-dependent regulator of chromatin, A-like 1 (SMARCAL1) as a genome maintenance protein. First, I introduce a functional genomic screen designed to identify novel genome maintenance genes. This screen led to the identification of SMARCAL1 and is the foundation for my project, providing the preliminary evidence to support that SMARCAL1 functions to maintain genome integrity. Next, I investigate the specific genome maintenance activity of SMARCAL1 and find that localization of its enzymatic activity to stalled replication forks is required for genome integrity during DNA replication. Finally, I explore how phosphorylation of SMARCAL1 regulates its function. Importantly, mutations in SMARCAL1 cause the human disease Schmike immuno-osseous dysplasia (SIOD). The research presented herein suggests that the phenotypes of SIOD are, in part, due to defects in SMARCAL1 genome maintenance activity.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-05252012-151148 |
| Date | 15 June 2012 |
| Creators | Robbins, Carol Bansbach |
| Contributors | Larry Marnett, Christine Eischen, Brandt Eichman, David Cortez, Scott Heibert |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-05252012-151148/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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