Identification of genes involved in recombination-mediated telomere maintenance in yeast

Telomeres are structures that protect the ends of chromosomes from deterioration and fusion with other chromosomes. The enzyme telomerase ensures that the telomeres are extended and maintained at a proper length. In most human cells, telomerase levels are low, causing telomeres to shorten with each round of cell division. Cells with critically shortened telomeres are unable to continue dividing. This is thought to be a driver of aging, but also to act as a barrier to cancer development, as it limits the proliferative potential of cancer cells. Cancer cells use certain mechanisms to overcome this barrier. Most cancer cells (85-90%) express telomerase to counteract the shortening of telomeres. Other cancer cells (10-15%) do this by activating the Alternative Lengthening of Telomeres (ALT) mechanism. Much is still unclear about how ALT is activated in cancer cells. During my PhD, I used the model organism Saccharomyces cerevisiae (baker's yeast) to study this ALT mechanism. Yeast can also use ALT to maintain their telomeres; such yeast cells are called "survivors". I searched for and identified genes that are involved in survivor formation, some of which were not previously reported as being important in survivor formation. In particular, a few of these genes were known to regulate the intracellular levels of deoxynucleoside triphosphates (dNTPs), which are the building blocks of DNA. I subsequently showed that dNTP levels are increased early after inactivation of telomerase, and that this increase is important to generate survivors