Characterizing DNA secondary structure of hairpin-containing intermediates of the base excision repair pathway

Description

Abstract:
Regions of repetitive DNA, in particular trinucleotide repeats, are common throughout the human genome and are of interest as a source of genomic instability. DNA strands that have trinucleotide repeats, such as (CAG)n repeats can expand to yield a longer repeat tract. While the exact mechanism of expansion is still unknown, expansion is hypothesized to result from the ability of (CAG)n repeat DNA to form non-canonical secondary structures, including stem-loop hairpins. Hairpins are "hotspots" for DNA damage because the unpaired guanine in the loop of the hairpin is subject to oxidation, leading to an 8-oxo- 7,8 dihydroguanine lesion, which must be repaired. This project is focused on the Base Excision Repair (BER) pathway, which is responsible for repairing these oxidized base lesions. Within mixed sequence DNA, the enzymes involved in BER remove damaged bases and replace them to restore the integrity of the DNA sequence. DNA Ligase 1 typically completes the repair event, creating a new phosphodiester bond at the nick site in the DNA. However, (CAG)n repeat DNA leads to hairpin-containing intermediates which contain extra nucleotides. If DNA Ligase 1 is able to ligate these hairpin-containing strands, the repeat tract will be expanded. My project will be using chemical probes that react with solvent exposed bases to sequence and characterize the secondary structure of proposed hairpin-containing intermediates of the Base Excision Repair pathway.

Citation

Bolton, Elizabeth, "Characterizing DNA secondary structure of hairpin-containing intermediates of the base excision repair pathway" (2015). Summer Research Symposium. Brown Digital Repository. Brown University Library. https://doi.org/10.26300/e1gz-3s08

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