Molecular mechanisms of telomere protection and poly(ADP-ribosyl)ation-regulated telomere length homeostasis

An elaborate machinery constantly detects and repairs damage to our DNA. While a break of both strands of the DNA double helix is dangerous and needs to be repaired rapidly, normal chromosome ends, which resemble DNA breaks, do not trigger the same response. Special sequences at the ends of chromosomes, the telomeres, are packaged by proteins that collectively avert the damage response. At the same time, telomeres serve as templates for the telomerase enzyme, which maintains telomeres at a constant length in long-lived cells. Telomere packaging, however, impedes the access and function of telomerase. 

A protein known as tankyrase orchestrates telomere packaging and extension so they can occur simultaneously. We will use electron microscopy and biochemistry to study how this occurs and why defects in telomere packaging can lead to cancer and heritable diseases.