Author ORCID Identifier
https://orcid.org/0000-0002-9290-6605
Date of Award
Fall 12-16-2020
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Chemistry
First Advisor
Ivaylo Ivanov
Second Advisor
Donald Hamelberg
Third Advisor
Kathryn B. Grant
Abstract
High fidelity maintenance of the genome is imperative to ensuring stability and proliferation of cells. The genetic material (DNA) of a cell faces a constant barrage of metabolic and environmental assaults throughout the its lifetime, ultimately leading to DNA damage. Left unchecked, DNA damage can result in genomic instability, inviting a cascade of mutations that initiate cancer and other aging disorders. Thus, a large area of focus has been dedicated to understanding how DNA is damaged, repaired, expressed and replicated. At the heart of these processes lie complex macromolecular dynamics coupled with intricate protein-DNA interactions. Through advanced computational techniques it has become possible to probe these mechanisms at the atomic level, providing a physical basis to describe biomolecular phenomena. To this end, we have performed studies aimed at elucidating the dynamics and interactions intrinsic to the functionality of biomolecules critical to maintaining genomic integrity: modeling the DNA editing mechanism of DNA polymerase III, uncovering the DNA damage recognition/repair mechanism of thymine DNA glycosylase and linking genetic disease to the functional dynamics of the pre-initiation complex transcription machinery. Collectively, our results elucidate the dynamic interplay between proteins and DNA, further broadening our understanding of these complex processes involved with genomic maintenance.
DOI
https://doi.org/10.57709/20345880
Recommended Citation
Dodd, Thomas, "Computational Investigations of Biomolecular Mechanisms in Genomic Replication, Repair and Transcription." Dissertation, Georgia State University, 2020.
doi: https://doi.org/10.57709/20345880
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