Formation and enzyme processing of 5-carboxamido- 5-formamido-2-iminohydantoin, a major oxidation product of guanine in DNA

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Title Formation and enzyme processing of 5-carboxamido- 5-formamido-2-iminohydantoin, a major oxidation product of guanine in DNA
Publication Type dissertation
School or College College of Science
Department Chemistry
Author Alshykhly, Omar R.
Date 2015
Description Oxidative damage to DNA, a factor in cancer, mutation, and aging, is attributed to reactive oxygen species (ROS). ROS are formed exogenously and endogenously and attack DNA showing a preference for reaction with 2-deoxyguanosine (dG) sites. In present work, dG was oxidized by HO. that was generated via iron-Fenton reaction or by X-ray radiolysis of water. Under aerobic conditions and in presence of reductant, the product 5-carboxamido-5-formamido-2-iminohydantoin (d2Ih) was the major lesion formed. The above prescribed conditions are mimic to cellular conditions. DNA polymerase and base excision repair processing of 2Ih lesion has been evaluated in this study. 2Ih bears a stereocenter in the base and was found as two diasteromers, (R)-2Ih and (S)-2Ih. Single nucleotide insertion opposite (R)-2Ih and (S)-2Ih in the template strand catalyzed by the DNA polymerases Klenow fragment exo?, DPO4, and Hemo KlenTaq demonstrate these lesions cause point mutations. Specifically, they promote thre
Type Text
Publisher University of Utah
Subject Base excision repair; DNA damage; Fenton reaction; Guanine oxidation; Reactive oxygen species; X-ray
Dissertation Name Doctor of Philosophy
Language eng
Rights Management ©Omar R. Alshykhly
Format application/pdf
Format Medium application/pdf
Format Extent 27,159 bytes
Identifier etd3/id/3988
ARK ark:/87278/s6t75rsp
Setname ir_etd
ID 197538
Reference URL https://collections.lib.utah.edu/ark:/87278/s6t75rsp
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