Document Type

Thesis

Degree

Master of Science (MS)

Department

Chemistry

First Advisor's Name

Yuan Liu

First Advisor's Committee Title

Committee Chair

Second Advisor's Name

Xiaotang Wang

Third Advisor's Name

David Becker

Keywords

DNA methylation, DNA demethylation, Base Excision Repair, DNA damage

Date of Defense

11-15-2013

Abstract

DNA methylation and demethylation are involved in regulation of gene expression. CpG clusters have been identified as hotspots of oxidative damages and mutagenesis. DNA base excision repair can remove oxidative DNA damage on CpG clusters and mediate an active DNA demethylation pathway. In this study, we examined the molecular mechanisms underlying interactions among DNA methylation, demethylation and BER. Our results demonstrated that a single 5-methylcytosine did not exhibit a significant effect on BER. Surprisingly we found that the abasic site completely inhibited the activity of thymine DNA glycosylase (TDG) leading to the sustainment of the mismatch efficiently extended by pol β. Interestingly, APE1 3’-5’ exonuclease could removed the mismatch. Our results demonstrate a molecular mechanisms underlying DNA base lesion and BER in maintenance of a normal DNA methylation pattern and a critical role of APE1 to combat pol β extension of the mismatch thereby reducing the introduction of mutagenesis.

Identifier

FI13120903

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