Access Type

Open Access Thesis

Date of Award

January 2012

Degree Type

Thesis

Degree Name

M.S.

Department

Nutrition and Food Science

First Advisor

Diane C. Cabelof

Abstract

Abstract

Role of Uracil DNA-Glycosylase and Folate

In the Repair of Oxidative Damage

By

Sarah Dubaisi

May2012

Advisor: Dr. Diane Cabelof

Major: Nutrition and Food Science

Degree: Masters of Science

The impact of DNA damage on genomic integrity has been widely investigated due to its association with cancer and ageing. DNA repair pathways play a critical role in preserving the genomic integrity and protecting the cells against DNA damage caused by oxidative stress and folate deficiency. Base Excision Repair (BER) is one of the major pathways involved in the cellular response to DNA damage, primarily the damage caused by oxidative stress. UNG genotype and folate were found to have an impact on the ability of the cell to repair DNA damage.

The present study was designed to examine the impact of uracil-DNA-glycosylase and folate deficiency on the cell cycle progression and the cells capacity to repair DNA damage in the presence of carcinogenic agents such as H2O2 and MTX, using the doubling time, cytotoxicity, and uracil accumulation assays. Based on our data, we can conclude that folate deficiency and UNG genotype stalls cell cycle progression, induces uracil accumulation, and reduces the cells ability to repair the DNA damage.

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