Title

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

Poster Number

15

Lead Author Affiliation

Chemistry

Lead Author Status

Masters Student

Second Author Affiliation

Chemistry Department

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.

Purpose

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

Method

We incorporated a 5-acetaldC base into DNA oligonucleotides using an automated DNA synthesizer and studied its biophysical and biochemical properties using UV melting denaturation and circular dichroism.

Results

UV melting denaturation and circular dichroism experiments suggested that the presence of this lesion had little destabilization and conformational distortions of duplex DNA. The lesion did not alter the ability of the polymerases to extend their DNA template fully. Results from single-nucleotide extension experiments revealed that the effect of the lesion on DNA polymerases was dependent on the position of the primers.

Significance

This work is important because it allows us to understand the effects that exposure to these environmental toxins can have on the cell.

Location

DUC Ballroom A&B

Format

Poster Presentation

Poster Session

Afternoon

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Apr 29th, 1:00 PM Apr 29th, 3:00 PM

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

DUC Ballroom A&B

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.