Carol Greider, Ph.D.
Telomerase and Telomere Length Regulation: From
Basic Principles to Cancer
Telomeres are required at chromosome ends for stability and to allow the complete replication of linear chromosomes. Telomerase is a ribonucleoprotein polymerase that synthesizes telomere repeats onto chromosome ends. Evidence from yeast and mammalian cell cultures suggests that telomerase is required for telomerase length maintenance, in the absence of telomerase chromosomes shorten progressively. Telomerase activity is often not detected in a human primary cells and tissues, while tumor-derived cell lines and many tumors samples contain detectable telomerase activity. The presence of telomerase activity and short telomeres in tumors suggested that inhibiting telomerase may be an effective cancer treatment. Our lab is focused on understanding in detail the biochemical mechanism of telomerase elongation, and the regulation that allows telomere length maintenance in vivo. In recent years we have cloned a number of telomerase components and have developed assays to study the biochemistry of the Tetrahymena and mammalian telomerase enzymes. We have also begun to dissect the pathways that regulate telomerase in mammalian cells through understanding the cell cycle and developmental regulation of the enzyme. Finally in collaboration with Dr. Ronald DePinho's lab at the Albert Einstein College of Medicine, we have generated a mouse that lacks telomerase activity. This telomerase "knock-out" mouse is helping us to understand the role of telomerase and telomere maintenance in mouse development and in cancer.