Research Interest:

Nucleic acid structure and function

We study nucleic acid structure and specific recognition of nucleic acids by proteins. Our primary research tool is multidimensional nuclear magnetic resonance (NMR) spectroscopy. We also utilize a range of molecular biology, biochemical, and biophysical techniques including X-ray crystallography. These techniques are used to determine the three-dimensional structures of DNA and RNA, to investigate their interactions with various proteins and ligands, and to study nucleic acid folding.

One major area of investigation involves structural and functional studies of nucleic acids and proteins involved in eukaryotic ribosome biogenesis and in trafficking through the nucleolus. Major proteins and RNAs which we are investigating are nucleolin and its interaction with pre-ribosomal RNA, yeast RNAse III, and box H/ACA snoRNPs, which are involved in pseudouridylation of sites on the rRNA. We are also interested in the structure of DNA telomeres and their synthesis by telomerase. We determined the first structure of a telomere repeat DNA and showed that it forms a four-stranded G-quadruplex structure. Our current work is focused on determining structures of sub-domains of the telomerase RNA, including the H/ACA box region which targets telomerase to the nucleolus or Cajal bodies, and their interaction with telomerase proteins.

Another area of interest is in the interaction of non-sequence specific HMG box proteins with DNA. These proteins have been shown to play roles in DNA recombination, repair, activation and repression of transcription as well as nucleosome assembly and disassembly. We are investigating how the yeast HMG box protein NHP6A interacts with DNA and modulates the affects of the anticancer drug cis-platin. We are also investigating the interactions of the DNA nucleotide excision repair protein HHR23A with other cellular DNA repair proteins, the ubiquitin/proteosome pathway, and HIV-1 Vpr.

Finally, we are interested in fundamental questions of nucleic acid folding and cation interactions. We are also involved in NMR methods development to augment our studies of nucleic acid structure and cation interactions.