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THE S. POMBE MST1 HISTONE ACETYLTRANSFERASE IS REQUIRED FOR
GENOME STABILITY
by
Rebecca Lynn Nugent
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree of
DOCTOR OF PHILOSOPHY
(MOLECULAR BIOLOGY)
August 2010
Copyright 2010 Rebecca Lynn Nugent
Object Description
| Title | The S. pombe Mst1 histone acetyltransferase is required for genome stability |
| Author | Nugent, Rebecca Lynn |
| Author email | rnugent@usc.edu; rebanug@gmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Molecular Biology |
| School | College of Letters, Arts and Sciences |
| Date defended/completed | 2010-06-16 |
| Date submitted | 2010 |
| Restricted until | Unrestricted |
| Date published | 2010-08-09 |
| Advisor (committee chair) | Forsburg, Susan L. |
| Advisor (committee member) |
Aparicio, Oscar Rice, Judd |
| Abstract | Within the cell DNA exists as chromatin, a complex mass of nucleic acids and proteins. Chromatin is highly structured and is compacted through the interaction of double stranded DNA with histone proteins, to form a nucleosome. Histones are post- translationally modified on the amino acids of their N-terminal tails to create a heritable epigenetic code. Histone acetylation regulates the interaction between DNA and histones in nucleosomes. Histone acetyltransferases are the enzymes that transfer acetyl groups on to histones.; S. pombe (Sp) Mst1 is a member of the MYST family of histone acetyltransferases (HATs) and is the likely orthologue of human TIP60 and S. cerevisiae Esa1 (KAT5). The MYST family of HATs has roles in transcriptional regulation and DNA damage repair. I show SpMst1 is necessary for response to DNA damage. Mst1 was found to interact with a wide-variety of proteins through a yeast 2-hybrid experiment: I confirmed the interaction of Mst1 and Rad22. I also found evidence for increased endogenous DNA damage in mst1 mutant cells. I show Mst1 functions within DNA damage checkpoint pathway.; I found that MYST and GNAT family HATs have significant functional overlap in regards to induced cellular stress, transcription and acetylation targets. Specifically the MYST family HAT SpMst2 and GNAT family HAT SpGcn5 each acetylate histone H3 lysine 14.; Finally I show that histone acetylation is necessary for proper centromere architecture. Mst1 is genetically placed to function at the central core of the centromere. In the absence of Mst1 the kinetochore, localization is disrupted. The kinetochore is a complex of proteins that link the chromosomes and microtubules during cytokinesis. Data suggest this is related to histone H4 acetylation. |
| Keyword | Mst1; MYST; fission yeast; genome stability; histone acetyltransferase; chromatin; centromere; DNA damage repair; transcription |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m3355 |
| Rights | Nugent, Rebecca Lynn |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Nugent-3942 |
| Archival file | uscthesesreloadpub_Volume51/etd-Nugent-3942.pdf |
Description
| Title | Page 1 |
| Full text | THE S. POMBE MST1 HISTONE ACETYLTRANSFERASE IS REQUIRED FOR GENOME STABILITY by Rebecca Lynn Nugent A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY (MOLECULAR BIOLOGY) August 2010 Copyright 2010 Rebecca Lynn Nugent |
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