Title

DNA Lesions Produced from the Reaction of Diols and 5-Formylcytosine and Their Effects on DNA Replication

Poster Number

12a

Lead Author Affiliation

Pharmaceutical and Chemical Sciences

Lead Author Status

Masters Student

Second Author Affiliation

Chemistry

Second Author Status

Faculty

Introduction

The cytosine bases of DNA are methylated at various places on the chromosome. This methylation is most prevalent in the promoter regions of inactive genes, indicating that methylation serves as a mechanism of control of gene expression (Epigenetics). While 5-methylcytosine (5-mC) is the main epigenetic base, other bases resulting from oxidation of 5-mC exist such as 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC), and 5-carboxycytosine (5-caC). 5-fC is of particular importance due to its reactive nature. Diols are examples of nucleophilic compounds that could react with the formyl group of 5-fC to yield a cyclic acetal (5-acetaldC). The exposure level of diols such as ethylene glycol and 1,3 propanediol to human is high because they are common environmental toxins from antifreeze, textiles, and many other industrial products.

Purpose

The presence of 5-acetaldC in DNA could affect the biological functions of DNA enzymes. In the present work, we sought to investigate the effects of 5-acetaldC on DNA replication.

Method

The ability of these lesions to form was first verified using mass spectrometry. We then incorporated a 5-acetaldC base into DNA oligonucleotides using an automated DNA synthesizer and studied its biophysical and biochemical properties. Both single lesion and tandem lesion sequences were studied.

Results

The single lesion did not alter the ability of the polymerases to extend their DNA template fully. Results from single-nucleotide extension experiments revealed that fidelity is also maintained when extending across a single lesion. Single-nucleotide extension experiments with the tandem lesion sequence revealed the potential for mismatched base pairs, making this lesion potentially mutagenic.

Significance

Based on the results this lesion is potentially mutagenic.

Location

DeRosa University Center

Format

Poster Presentation

Poster Session

Afternoon 1pm-3pm

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DNA Lesions Produced from the Reaction of Diols and 5-Formylcytosine and Their Effects on DNA Replication

DeRosa University Center

The cytosine bases of DNA are methylated at various places on the chromosome. This methylation is most prevalent in the promoter regions of inactive genes, indicating that methylation serves as a mechanism of control of gene expression (Epigenetics). While 5-methylcytosine (5-mC) is the main epigenetic base, other bases resulting from oxidation of 5-mC exist such as 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC), and 5-carboxycytosine (5-caC). 5-fC is of particular importance due to its reactive nature. Diols are examples of nucleophilic compounds that could react with the formyl group of 5-fC to yield a cyclic acetal (5-acetaldC). The exposure level of diols such as ethylene glycol and 1,3 propanediol to human is high because they are common environmental toxins from antifreeze, textiles, and many other industrial products.