Grant: Project Grant

The human body is composed of trillions of cells, the longevity of which is dependent on the balance between forces that promote or stall growth. On one hand, early cell stalling is known as senescence and it can lead to premature cellular aging if kept unchecked. On the other hand, uncontrolled cell growth can lead to cancer. Critical to the cell's ability to strike the right balance between growth and senescence are highly repetitive DNA regions known as ribosomal DNA (rDNA) repeats. These rDNA repeats harbour genes from which molecules known as ribosomal RNA (rRNA) are produced. rRNA production is critical to general protein production and cell growth. In contrast, DNA damage at rDNA repeats can lead to premature senescence. How cells strike the right balance between the impact of rDNA repeats on growth and senescence remains unclear. Here, we pursue new findings suggesting that a new protein complex localizes to poorly understood spacers located between rDNA units in order to optimize protein production and growth while limiting DNA damage and cell senescence. We have two main objectives. First, we wish to decipher the rDNA-regulatory role of this complex at rDNA in order to reveal new mechanisms that are critical to the regulation of growth and senescence in human cells. Second, we will exploit the new knowledge of this mechanism to preferentially induce early senescence and limit tumorigenic potential in breast cancer cells. Overall, this work will uncover key health-related knowledge pertaining to the balance between cell growth and senescence while revealing how it can be exploited to combat deadly human diseases.