Dissertation
EXAMINING THE REGULATION OF DNA EXCISION REPAIR AND MUTAGENESIS IN CHROMATIN
Washington State University
Doctor of Philosophy (PhD), Washington State University
01/2022
DOI:
https://doi.org/10.7273/000004520
Handle:
https://hdl.handle.net/2376/125010
Abstract
Eukaryotic cells must rapidly sense and repair damage in a genome that is organized intochromatin, an intricate assemblage of DNA wrapped around a histone protein octamer
approximately 1.7 times to form a structure known as the nucleosome. Nucleosomes serve a
multifaceted function: in addition to compacting the eukaryotic genome to fit within the spatial
confines of the nucleus, they are responsible for facilitating tight regulation of DNA-templated
processes such as replication, transcription, and DNA repair. Moreover, post-translational
modification of the individual histone proteins constituting the nucleosome provide an interface
by which these processes may be regulated, thereby potentially enabling more rapid repair of
lesions located within nucleosomes. Inefficient repair of DNA damage in nucleosomes and
higher order chromatin states can lead to elevated rates of mutagenesis, which can promote
carcinogenesis. In this dissertation, we utilized Saccharomyces cerevisiae as a model system to
elucidate how histone post-translational modifications such as acetylation and methylation
regulate DNA excision repair and mutagenesis within chromatin. We first conducted a survey of
histone acetyltransferase (HAT) complexes in which we identified the NuA4 HAT complex as
playing a critical role in regulating repair of UV-induced DNA lesions through the nucleotide excision repair (NER) pathway. Second, we explored mutation signatures associated with UV-A
and UV-B light-induced DNA photolesions in yeast and characterized the impact of
transcription-coupled NER (TC-NER) on mutational strand asymmetry. Finally, we investigated
the regulatory role of histone methylation by the Set2 methyltransferase in NER, demonstrating
its involvement specifically in TC-NER.
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Details
- Title
- EXAMINING THE REGULATION OF DNA EXCISION REPAIR AND MUTAGENESIS IN CHROMATIN
- Creators
- Dalton Anthony Plummer
- Contributors
- John Wyrick (Advisor)Lisa Gloss (Committee Member)Steven Roberts (Committee Member)John Hinz (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Molecular Biosciences, School of
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 224
- Identifiers
- OCLC#: 1365273135; 99900882926301842
- Language
- English
- Resource Type
- Dissertation