Telomerase Activity Enhancement in Saccharomyces cerevisiae

Telomeres are located at the ends of eukaryotic linear chromosomes and are composed of repeated nucleotide sequences. One of their main functions is to protect chromosomal ends from being damaged. Telomeres cannot be completely copied during DNA replication so they gradually shorten during each replication cycle in what is known as the “end replication problem”. To counteract this problem, the RNA dependent enzyme complex telomerase works to extend telomeres and help protect the ends of chromosomes. Telomeres and the telomerase enzyme are heavily involved in the aging process and cancer progression. Telomeres gradually shorten with age and eventually become so short that cells begin to senese and undergo apoptosis. Most cancers avoid senescence and apoptosis by activating telomerase at an excessive rate to reduce telomere shortening. The structure and function of telomerase RNA is not well understood. Most past research has focused on identifying loss-of-function mutations rather than identifying gain-of-function mutations. We set out to identify gain-of-function mutations to help us learn more about telomere length and telomerase and how they relate to aging and cancer. We screened nearly 10,000 colonies and identified 32 possible gain-of-function candidates that we are currently in the process of verifying.We used Saccharomyces cerevisiae as the model organism in our gain-of-function genetic screen to identify mutations that lengthen telomeres by increasing telomerase activity. The gain-of-function mutants identified through our screen will further enhance our understanding of how significant increasing telomerase activity could be to human health as a whole.https://scholarworks.moreheadstate.edu/celebration_posters_2022/1006/thumbnail.jp