Research Interests

Although most biological catalysts are proteins, we and others have found that in some cases RNA (a form of genetic material) can act as an enzyme. A major goal of our work is to understand mechanisms of RNA (ribozyme) catalysis at both the chemical and biological levels. Self-splicing group I introns are a major experimental system. Chemical synthesis allows us to change single atoms within large RNAs, and the effects of these substitutions on ribozyme folding, substrate binding, and the chemical cleavage step can be differentiated. x-ray crystallography has proven invaluable for understanding structure-function relationships in proteins. The crystallization and solution of the structure of a large domain of the Tetrahymena ribozyme made it possible to show the level of RNA folding revelant to large catalytic RNAs and provides an excellent basis for planning future biochemical and x-ray crystallographic experiments. We also study the structure and replication of telomeres, the natural ends of linear chromosomes, in biological systems with unusually large numbers of linear DNA molecules in their macronuclei (Oxytricha and Euplotes) and in yeast, which permit a genetic approach. The long-term goal is to contribute to the understanding of the mechanisms and regulation of telomerase, the RNA-protein complex that replicates telomeres.

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Section 21: Biochemistry