Nucleic acid structure – Xray and NMR

Three-dimensional image showing DNA binding and nucleotide flipping by the human DNA repair protein AGT. We use NMR and X-ray crystallography to study the structural properties of nucleic acids including base pair mismatches in DNA and their implications for DNA repair. This produced a series of publications including the structures of DNA duplexes containing G.T mismatches (View paper) and A.C mismatches (View paper). Our studies highlighted the fact that mispaired bases form distinct structures and cause minimal distortion to the overall conformation of the DNA duplex. Therefore enzymatic recognition of modified base pairs in living systems must depend upon subtle differences at the molecular level. We also recently solved the structures of DNA duplexes containing the epigenetic base 5-formyl C to determine its effects on conformation at high resolution (View Paper)