Effect of base lesions on duplex DNA

BIOL 200

Amy Rumora, aerumora@mtholyoke.edu, Anne Malhowski, and Megan E. Nunez. Department of Chemistry, Mount Holyoke College, 50 College Street, South Hadley, MA 01075
DNA is subjected to a barrage of endogenous and exogenous agents that cause permanent changes to its sequence and structure. This covalently damaged DNA must be restored to prevent mutations from persisting, but it is not clear how cellular repair machineries selectively recognize small modifications to the DNA bases buried within the double helix. We investigated DNA oligonucleotides containing a base lesion to determine what makes them recognizable. We examined base pair accessibility and duplex destabilization around lesions using small, reactive chemical probes, and measured the thermodynamics of duplex stability to determine the extent to which the lesion weakens the integrity of the double helix itself. Finally, we explored DNA dynamics around DNA lesions using NMR to determine whether the rate of DNA "breathing" is different around base lesions. The combination of these experiments generates a complex and interesting picture of the changes induced by base lesions within B-form DNA.
 

Frontiers in Chemical Biology
5:00 PM-7:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Biological Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007