Grant: Project Grant

Human chromosome ends are protected from damage by a stretch of repetitive DNA sequence known as telomeres. In healthy mortal cells, telomere DNA is gradually shortened during successive rounds of replication as a cell ages, and ultimately instructs cells to naturally terminate. In cancerous cells the enzyme telomerase ensures maintenance of a stable telomere length and therefore enables the indefinite growth and uncontrolled division characteristic of tumor formation. Active telomerase is diagnostic of cancer progression, as has been identified in the vast majority of malignant cancers. In this proposal, we seek to understand the regulation of telomerase by enzymes known as helicases that exert their effects through prevention of proper telomerase assembly. We will use an integrated experimental approach involving high-resolution structural biology, biochemical analysis, and functional methodologies. Our work aims to provide a template for the rational design of therapeutics to attenuate telomerase activity.