2026-09-20T09:34:23.045851Zhttps://opus.uleth.ca/server/oai/requestoai:opus.uleth.ca:10133/50932019-06-28T15:39:48Zcom_10133_3346com_10133_1com_10133_296col_10133_3347col_10133_298
ULethbridge OPUS Repository
supervisor
Wetmore, Stacey D.
author
Sowlati-Hashjin, Shahin
author
University of Lethbridge. Faculty of Arts and Science
2018-05-02T15:25:01Z
2018-05-02T15:25:01Z
2018
https://hdl.handle.net/10133/5093
Formation of guanine oxidation products is among the most frequently occurring DNA damaging events, and has been suspected to be related to aging, Alzheimer’s disease and various types of cancer. Guanine oxidative products are removed and replaced through the base excision repair (BER) pathway, which involves several enzymes including DNA glycosylases. BER is initiated when a DNA glycosylase detects a lesion and removes the damaged nucleobase. The present thesis employs computational chemistry to investigate the formation mechanisms of two guanine oxidation products, namely 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) and 7,8-dihydro-8-oxoguanine (OG). Moreover, several steps during the repair processes catalyzed by human (hOgg1) and bacterial (FPG) DNA glycosylases, including the lesion recognition, base removal, DNA backbone cleavage, and hydrolysis of the resulting DNA‒enzyme complex, are investigated using quantum mechanical and molecular dynamics approaches. The atomic-level details provided by these calculations show the differences in the recognition and removal mechanisms catalyzed by human and bacterial glycosylases.
en_US
DNA repair
DNA repair--Computer simulation
DNA damage
Oxidation
oxidation of guanine
base excision repair
computer modelling
DNA glycosylases
Computational investigation of oxidative damage to guanine: formation, recognition and removal by DNA repair enzymes in humans and bacteria
Thesis
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URL
http://localhost:4000/bitstreams/0e723efc-7965-4074-9cd6-c0380a5695d5/download
File
MD5
09be7e88173b592c8077c11e78a674ef
13201381
application/pdf
Sowlati-Hashjin_Shahin_PHD_2018.pdf
URL
http://localhost:4000/bitstreams/1c7145bb-857c-48b1-be94-3b1f17c4837b/download
File
MD5
1af0a70fa2a8ae78fa69e82c6b0b59f1
566558
text/plain
Sowlati-Hashjin_Shahin_PHD_2018.pdf.txt