Topic Overview:

O’Sullivan explores how telomeres are exploited as a means to ensure unlimited growth of cancer cells. Telomeres are specialized structures located at the ends of chromosomes. In normal cells, telomeres are eroded to a threshold limit that causes cells to cease dividing. Cancer cells bypass this threshold to uncontrolled proliferation by activating mechanisms that maintain telomere length. Most achieve this by up-regulating the expression of telomerase. However, a significant number of cancers do so via the regulated exchange of telomeric DNA between chromosomes in a pathway termed alternative lengthening of telomeres (ALT). While much is known about the telomerase-mediated mechanism of telomere length maintenance, the answers to why and how the ALT pathway is initiated have eluded understanding. O’Sullivan’s goal is to identify the key events that trigger the ALT pathway and to decipher the molecular characteristics and mechanisms of telomere maintenance by the ALT pathway in cancer.