Grant: Project Grant

In order to properly grow and divide, normal cells must maintain the integrity of their genome. Telomeres cap the ends of chromosomes and are essential to maintain their stability. Telomere shortening leads to genomic instability and favors the rise of cancers. In most eukaryotes, telomerase is a specialized enzyme used to elongate telomeres. Most of our knowledge on telomerase relies on the detection of its activity in large populations of cells. However, little is known about the behavior of telomerase in single cells, as it acts on a single telomere. For this purpose, we developed an assay to image both telomerase molecules and telomere in single living cells, using the budding yeast as a model organism. Using this approach, the events leading to the recruitment of telomerase at a single short telomere will be studied in real time, in single cells. We will particularly focus on the role of sister telomeres cohesion during telomerase recruitment at short telomeres. We will explore how telomerase is regulated in a telomere-specific manner by focusing especially on its interaction with telomeric repeat-containing noncoding RNA (TERRA). Finally, we will use live cell imaging to study the dynamics of telomerase molecules and their recruitment at telomeres in living human cancer cells. Identifying the pathways involved in the regulation of telomerase and telomeres will help understand how tumors arise and develop into cancer, and also reveal new potential targets for cancer therapy.