Grant: Operating 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. Our laboratory is using the budding yeast as a model organism to further understand how cells regulate their telomerase in order to maintain the telomeres at the extremities of their chromosomes. Most of our knowledge on telomerase relies on the detection of telomerase 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 recently developed an assay to study telomerase molecules in single living cells. Using this approach, the factors involved in the accumulation of telomerase in the nucleus will be identified. The events leading to the recruitment of telomerase at a single short telomere will be studied in real time, in single cells. Finally, we will explore how telomerase is regulated in a telomere-specific manner by focusing especially on telomeric repeat-containing RNA (TERRA). For now, due to its powerful genetics and cell biology tools, such study can only be performed in yeast. However, as in humans, disruption of telomerase trafficking in yeast is known to result in abnormal telomeres and in an increased instability of the genome. Identifying the pathways involved in the regulation of telomerase and telomeres will help to understand how tumors arise and develop into cancer, and also reveal new potential targets for cancer therapy.