The Stone Research Group combines the use of biochemical and structural methods with newly emerging single-molecule techniques to probe the dynamics of protein-nucleic acid interactions and the molecular mechanisms of biological motors. Our current area of focus is the structure and function of the telomerase ribonucleoprotein, an RNA-dependent DNA polymerase that maintains genomic stability by synthesizing repetitive DNA sequences at chromosome termini. These short DNA repeats provide the foundation for specialized chromatin structures, called telomeres, which prevent deleterious chromosome fusion events by differentiating chromosome ends from sites of DNA damage. It has been shown that telomere length typically decreases with every round of cell division, leading to the so-called ‘molecular clock’ hypothesis, wherein telomere length serves as a signal to control cellular lifespan. This notion is consistent with the finding that active telomere DNA synthesis is normally restricted to rapidly dividing cell types such as stem cells and the majority of human cancers. Our research seeks to elucidate physical mechanisms governing telomere length regulation, and in turn establish a conceptual framework within which to develop novel diagnostic and therapeutic strategies for human disease.
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