Insights into how the structural features of DNA adducts dictate local helical conformation and repairability: a computational study
No Thumbnail Available
Date
2024
Authors
Kung, Ryan W.
University of Lethbridge. Faculty of Arts and Science
Journal Title
Journal ISSN
Volume Title
Publisher
Lethbridge, Alta. : University of Lethbridge, Dept. of Chemistry and Biochemistry
Abstract
DNA damage occurs regularly and results in various biological consequences,
including cancer. One specific type of DNA damage is the formation of adducts, which
arise from various sources, including cigarette smoke and pesticides. The local helical
structure of adducted DNA is dictated by the chemical composition of the lesion.
Furthermore, various known conformations of adducted DNA have been shown to
differentially impact DNA repair and replication. Although this underscores how the lesion
dictates biological outcomes, structure–function relationships have yet to be fully explored.
Thus, this thesis uses computational modelling to examine the complex interplay between
the adduct chemical composition (e.g., bulky moiety shape, adduct linker type, and lesion
number) and the resulting damaged DNA structure and lesion mutagenicity. Overall, novel
trends in the helical conformation and lesion repairability as a function of the chemical
structure of the DNA adduct are uncovered, which have implications in the severity of the
long-term biological consequences.
Description
Keywords
computational chemistry , DNA damage , MD simulations , DFT calculations , DNA repair , DNA adducts