Direct Observation of Shelterin Dynamics and T-loop Formation at Telomeres.

Telomeres protect the ends of linear chromosomes, solving the end-replication problem and preventing activation of DNA damage responses which would otherwise result in chromosome fusions. At the core of telomere function is a striking dichotomy: protection and compaction of telomeric ends is crucial for chromosomal stability, however telomeric ends must also be replicated and accessed by telomerase to prevent excessive shortening. Telomere length regulation is vital to human health; telomeres shorten as we age, with rapid shortening resulting in premature ageing, but this also prevents uncontrolled cell replication, acting as a key barrier to cancer development. The telomere bound Shelterin complex is essential for end-protection, through T-loop formation, and for telomere maintenance, via telomerase recruitment. However, how Shelterin orchestrates these two processes remains an unanswered question central to telomere homeostasis.