Grants awarded

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

Grantholder:

Dr Sebastian Guettler

Institute of Cancer Research

United Kingdom

There is an elaborate machinery that 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 resemble breaks in DNA but do not trigger the same response. The special sequences at chromosome ends, known as telomeres, are packaged by proteins that avert the damage response. The telomerase enzyme maintains telomeres at a constant length in long-lived cells. Telomere packaging, however, impedes the access and function of telomerase. This is solved by a protein known as tankyrase, which 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.