Telomeres consist of short tandem repetitive sequences bound by specialised proteins. They help distinguish natural chromosome ends from DNA breaks in need of repair. Dysfunctional telomeres result in DNA damage checkpoint activation and cell cycle arrest. Telomeres progressively shorten due to incomplete DNA replication and nucleolytic degradation. When telomeres are critically shortened, cells can no longer divide, reaching a state known as replicative senescence. Shortening is counteracted by telomerase, the specialised reverse transcriptase that elongates telomeres. However, most human somatic cells do not express sufficient telomerase to prevent telomere shortening, which has been proposed as one reason why human individuals age. Replicative senescence is thought to function as a barrier to tumorigenesis since cancer cells need to maintain telomeres to continue proliferating.

Short tandem DNA repeat sequences account for approximately 3% of the human genome. These sequences are often difficult to replicate, are prone to expansion and contraction, and can cause chromosomal rearrangements. Expansion of 13 different short tandem repeat sequences is linked to approximately 50 diseases, including Huntington’s disease, Friedreich’s ataxia, and fragile X syndrome, while chromosomal rearrangements are a source of genetic diseases and cancer. Misregulation of telomeric repeats, a well-studied example of a short tandem repeat sequence, is a hallmark of both cancer and ageing.

We examine these processes at a molecular level using the budding yeast Saccharomyces cerevisiae, which is an ideal model organism given the highly conserved nature of these processes and the experimental advantages of the yeast system. We aim to identify relevant genes, and to determine their function and relationship with one another.