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Overview
The research program of the laboratory focuses on telomeres, the structures stabilizing the ends of the eukaryotic chromosomes, and the enzyme telomerase. The mechanisms of telomere and telomerase functions are under study in model organisms such as yeasts and in human cancer cells.

Research
Work in the Blackburn laboratory concerns the synthesis and function of telomeres, the ends of eukaryotic chromosomes. Telomeric DNA consists of tandem repeats of very simple sequences, one strand of which is synthesized by the ribonucleoprotein enzyme telomerase. Telomerase specifies the sequence of telomeric DNA by using a short sequence within the telomerase RNA moiety as the template for DNA synthesis. Thus, telomeric DNA is unusual in being an essential chromosomal element synthesized by copying an RNA sequence; that is, by reverse transcription.

Our goal is to understand the mechanism of telomerase action. One important question we wish to answer is how the functions of telomerase are divided between the RNA and protein moieties of the enzyme: the RNA not only provides the template, but also has other functions. Specific RNA mutations destroy catalysis by telomerase, while others cause aberrant telomerase active site functions. An interesting question is whether telomerase represents a relic of an ancestral RNA enzyme or ribozyme.

Our studies of telomere synthesis by telomerase in cells led to the finding that cell division is impaired by the actions of certain types of mutant telomerases. We seek to understand the full roles of telomerase in cell division processes. To this end, we are analyzing telomerases and telomeres in yeasts and in human cancer cells. We previously demonstrated that certain telomerase RNA mutants cause telomere shortening and cellular senescence in the ciliated protozoan Tetrahymena and yeasts and that chemical inhibitors of telomerase caused human cell telomeres to shorten. Other mutations of telomeres cause telomeres to get too long and become degraded, and can cause cells to stop dividing in anaphase in the cell cycle. We want to determine the mechanism of telomere capping that normally prevents such aberrant chromosome behaviors. We are currently testing the application of these findings for an anti-cancer strategy, using cancer cells including human breast, prostate and bladder cancer cells.