Lessons From Yeast: Mechanisms of Telomere Length Regulation

Telomeres are sequences at chromosome ends that distinguish the natural end from a DNA break. Telomeres shorten at each round of cell division because the replisome cannot completely copy both DNA strands to the very end. This shortening is counterbalanced by telomerase, which adds telomeric sequences de novo onto telomeres. The balance of shortening and lengthening is regulated to establish an equilibrium distribution of telomere lengths. If the equilibrium is perturbed, short telomeres trigger a DNA damage response that leads to cellular senescence or cell death. In humans, short telomeres cause age-related degenerative disease, while long telomeres protect against senescence and allow the continued growth of cancer cells. To target the telomere in human disease, we need a more complete understanding of how telomere length is regulated. Here, we describe pathways that regulate telomere length with a focus on the fundamental mechanisms established over the last 40 years in the yeast Saccharomyces cerevisiae.