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Consequences of Oxidative DNA Damage...

Moe, May Myat,

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Consequences of Oxidative DNA Damage: Base-Pair Dissociation, Singlet Oxygenation and DNA-Protein Crosslinking /

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Consequences of Oxidative DNA Damage: Base-Pair Dissociation, Singlet Oxygenation and DNA-Protein Crosslinking // May Myat Moe.
作者:	Moe, May Myat,
面頁冊數:	1 electronic resource (125 pages)
附註:	Source: Dissertations Abstracts International, Volume: 86-06, Section: B.
Contained By:	Dissertations Abstracts International86-06B.
標題:	Chemistry. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31640516
ISBN:	9798346878582

Consequences of Oxidative DNA Damage: Base-Pair Dissociation, Singlet Oxygenation and DNA-Protein Crosslinking /
Moe, May Myat,

Consequences of Oxidative DNA Damage: Base-Pair Dissociation, Singlet Oxygenation and DNA-Protein Crosslinking /May Myat Moe. - 1 electronic resource (125 pages)

Source: Dissertations Abstracts International, Volume: 86-06, Section: B.

8-Oxo-2'-deoxyguanosine (OG) is a common DNA lesion resulting from oxidatively generated damage and pairs with complementary cytidine (C) in Watson Crick base-pairing within duplex DNA. The WC-OG·C lesion, if not recognized or repaired, not only leads to G⋅C→T⋅A transversion mutations (through Hoogsteen (HG) base pairing of OG⋅A), but also renders the base pair being more vlunerable to ionizing radiation and singlet oxygen (1O2) damage. Leveraging on our previous accomplishments on the study of gas-phase reactions of 1O2 with 2'-deoxyguanosine radical cations, my research thesis expanded to the investigation of reaction dynamics of 9-methyl-8-oxoguanine (9MOG) radical cations. The experiments of following projects were realized using tandem mass spectrometry coupled with electrospray ionization, followed by the detection of product ions and measurement of cross sections. Potential energy surface calculations, Rice-Ramsperger-Kassel-Marcus (RRKM) kinetic modeling and direct dynamic simulations were carried out to help interpret experimental findings.The first project has focused on the characterization of non-statistical base-pair dissociation, consisting of the radical cations 9-methyl-8-oxoguanine·1-methyl-cytosine [9MOG·1MC]•+, and [9MOG·9-methylguanine(9MG)]•+. This study has revealed that non-statistical dissociation links to intra-base pair proton transfer originating from the N1-H at the Watson-Crick edge of 9MOG, enhancing understanding towards the base-pair fragmentation assisted by proton transfer. Taking an account into base-pair dissociation of [9MOG·1MC]•+, the second project has explored the effect of intra-base pair proton transfer on singlet oxygenation of [9MOG·1MC]•+. The reactivity of [9MOG·1MC]•+ toward 1O2 is compared with the reactivity of two forms of 9MOG radicals to understand the influence of structural context. The third project has revealed the key intermediates and reaction mechanism involved in DNA-protein crosslinks using the model methylamine (mimics the ε-NH2 group of lysine) reaction with one-electron oxidized 9MG•+ and doubly oxidized [9MG - H]+. It turned out that [9MG - H]+ is more electrophilic and susceptible to crosslinking.

English

ISBN: 9798346878582Subjects--Topical Terms:

516420
Chemistry.
Subjects--Index Terms:

Base-pair radical cations

Consequences of Oxidative DNA Damage: Base-Pair Dissociation, Singlet Oxygenation and DNA-Protein Crosslinking /
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