Dissertation
The effects of nucleosome core particle packaging on DNA charge transport
Washington State University
Doctor of Philosophy (PhD), Washington State University
12/2006
DOI:
https://doi.org/10.7273/000005649
Abstract
Consequences of DNA oxidation can be critical to the healthy maintenance of genomic integrity. When left undetected or unrepaired, DNA oxidative lesions can contribute to various adverse health conditions including cancer, heart disease, and neuronal deterioration. Most DNA oxidative lesions are localized on guanine (G) residues due to the low ionization potential as compared to the other nucleotides found in DNA. One electron oxidation of G results in the formation of a guanine radical cation (G +), or an electron deficient hole, which then has several fates available to it. One fate is that it may react with a molecule in solvent (O2, H20, O2 -) to form an irreversible oxidative lesion. Another option for the G + is a nearly isoenergetic exchange with another G within a DNA base stack, thereby mobilizing the electron hole to a site other than where it originated. This mobile electron hole may then migrate over long distances on DNA (>200 ) before becoming irreversibly trapped. While this phenomenon has been extensively studied in B-form DNA systems, little has been done to explore the potential and/or consequences of these events in biological settings. I have taken the nucleosome core particle (NCP) as a biological model to investigate the dynamics of DNA charge transport (CT). Here I report the results of using an Anthraquinone (AQ) photooxidant to initiate DNA CT in NCPs using highly thermodynamic NCP positioning sequences (TG-motif and 601). My studies show that there are significant qualitative and quantitative differences in G damage distributions in both free DNA and reconstituted NCPs. I have also identified a unique DNA protein crosslink as a result of DNA CT. Additionally, I have observed a previously undiscovered phenomenon called protein mediated DNA CT. The results and interpretations of the data presented here will have profound impacts on future studies of DNA CT in biological systems.
Metrics
3 File views/ downloads
13 Record Views
Details
- Title
- The effects of nucleosome core particle packaging on DNA charge transport
- Creators
- Chad Christopher Bjorklund
- Contributors
- William B. Davis (Chair)
- Awarding Institution
- Washington State University
- Academic Unit
- School of Molecular Biosciences
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 175
- Identifiers
- 99901054531401842
- Language
- English
- Resource Type
- Dissertation