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Publication Date

2023-5

First Advisor

Cristina Suarez

Second Advisor

Elizabeth R. Jamieson

Document Type

Honors Project

Degree Name

Bachelor of Arts

Department

Chemistry

Keywords

Spiroiminodihydantoin (Sp) lesion, mismatch base pairing, oxidative DNA damage biomarker, Nuclear Magnetic Resonance (NMR), high performance liquid chromatography (HPLC), deoxyribonucleic acid

Abstract

Errors are often introduced to deoxyribonucleic acid (DNA), whether the nucleobases are incorrectly paired during replication or the nucleobase itself becomes oxidized by damaging agents. These errors are detected by the repair mechanisms of the human cell. However, when damaged DNA isn't successfully repaired, it can lead to many health problems, such as cancer. There have been prior studies on the structural and dynamic effects of DNA lesions and dynamic properties of mismatched bases, but much less is known about mismatch bases. Therefore, it is helpful to characterize the structure and dynamic of DNA duplex containing one pair of DNA mismatched bases to determine how they affect the double helix structure. As the base with the lowest reduction potential, guanine (G) is easily oxidized to produce 8-oxoguanine (8-oxoG) which leads to G → T transversion mutations, where a purine is being substituted by a pyrimidine. Further oxidation produces hyperoxidized guanine lesions, such as the (R/S) spirominodiydantoin (Sp) lesion. The presence of Sp lesion in normal DNA can lead to further transverse mutations resulting in DNA containing mismatch base pairs. Mismatched DNA, such as G-G instead of G-C in a DNA duplex, generally destabilizes the double helical structure by weakening the hydrogen bonding. This project focuses on the mismatched GG base pair effect on DNA through base pair opening studies using 1H Nuclear Magnetic Resonance (NMR) spectroscopy. The overarching goal of the lab is to combine mismatched base pair studies with lesion to further grasp the damage of both mutations effect on DNA. This would be done by an investigation of the Sp lesion’s effect on an 11-mer G-G mismatched DNA duplex compared to a control G-C 11-mer DNA duplex. This thesis will focus on a comparative study of the mismatched GG DNA and GC control DNA.

Rights

©2023 Jiayun Chen. Access limited to the Smith College community and other researchers while on campus. Smith College community members also may access from off-campus using a Smith College log-in. Other off-campus researchers may request a copy through Interlibrary Loan for personal use.

Language

English

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