Title

TDS, not so tedious: An efficient technique to study topological changes in modified G-quadruplex DNA

Lead Author Major

Biochemistry

Format

Oral Presentation

Faculty Mentor Name

Liang Xue

Faculty Mentor Department

Chemistry

Abstract/Artist Statement

The UV thermal difference spectrum (TDS) is a convenient and inexpensive tool for characterization of nucleic acid structures. It is obtained by taking the difference in the UV absorbance spectra of the unfolded and folded states of a given nucleic acid below and above its melting temperature. The specific shape of the spectra is distinctive for a given nucleic acid sequence/structure. Recently, it was reported (Angew. Chem. Int. Ed. 2011, 123, 10833-10836) that TDS spectra can be used to classify different types of G-quadruplex DNA topologies as well. G-quadruplex DNA is a unique DNA secondary structure that is formed by guanine rich nucleic acid sequences. The guanine nucleobase can associate through Hoogsteen hydrogen bonds to form a square planar structure called G-tetrad. The G-tetrads then stack on top of each other to give rise to G-quadruplex DNA. Such structures have been proposed to form at the ends of chromosomes i.e. the telomeric region containing the 5’-dTTAGGG repeats and play an important role in genomic integrity. Telomeric DNA is readily accessible by DNA damaging agents, leading to chemical modification of nucleobases such as 8-oxo-7,8-dihydroguanine (8-oxodG), 8- oxo-7,8-dihydroadenine (8-oxodA) and abasic sites. Herein, we report the use of TDS as a tool to study the effect of location and type of nucleobase modification viz. 8-oxodG, 8-oxodA and abasic sites, on the topological changes in G- quadruplex DNA structures.

Location

DeRosa University Center, Room 219

Start Date

21-4-2012 1:00 PM

End Date

21-4-2012 5:00 PM

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Apr 21st, 1:00 PM Apr 21st, 5:00 PM

TDS, not so tedious: An efficient technique to study topological changes in modified G-quadruplex DNA

DeRosa University Center, Room 219

The UV thermal difference spectrum (TDS) is a convenient and inexpensive tool for characterization of nucleic acid structures. It is obtained by taking the difference in the UV absorbance spectra of the unfolded and folded states of a given nucleic acid below and above its melting temperature. The specific shape of the spectra is distinctive for a given nucleic acid sequence/structure. Recently, it was reported (Angew. Chem. Int. Ed. 2011, 123, 10833-10836) that TDS spectra can be used to classify different types of G-quadruplex DNA topologies as well. G-quadruplex DNA is a unique DNA secondary structure that is formed by guanine rich nucleic acid sequences. The guanine nucleobase can associate through Hoogsteen hydrogen bonds to form a square planar structure called G-tetrad. The G-tetrads then stack on top of each other to give rise to G-quadruplex DNA. Such structures have been proposed to form at the ends of chromosomes i.e. the telomeric region containing the 5’-dTTAGGG repeats and play an important role in genomic integrity. Telomeric DNA is readily accessible by DNA damaging agents, leading to chemical modification of nucleobases such as 8-oxo-7,8-dihydroguanine (8-oxodG), 8- oxo-7,8-dihydroadenine (8-oxodA) and abasic sites. Herein, we report the use of TDS as a tool to study the effect of location and type of nucleobase modification viz. 8-oxodG, 8-oxodA and abasic sites, on the topological changes in G- quadruplex DNA structures.