Shelterin (the telosome) is a complex of six proteins that binds to telomeres and protects them from the DNA-repair systems. Without shelterin the cell would mistake the ends of chromosomes for breaks and try to "glue" them together, leading to chromosomal rearrangements.
The complex folds the end of the telomere into a loop (the t-loop), hides the single-stranded "tail" and controls when the enzyme telomerase is allowed access to the telomere.
The six subunits
The complex includes six proteins with a division of labour. TRF1 and TRF2 sit on the double-stranded telomere repeats and serve as the "foundation"; TRF2 also helps form the t-loop. POT1 binds the single-stranded 3' tail and shields it from nucleases. TPP1 is the only shelterin protein in direct contact with telomerase, and it is the one that brings the enzyme to the telomere when it needs to be lengthened. TIN2 serves as a "bridge", connecting TRF1, TRF2 and the TPP1–POT1 pair. RAP1 (paired with TRF2) suppresses inappropriate DNA repair.
How shelterin protects the ends
Shelterin's main job is to make sure the cell does not perceive the natural end of a chromosome as damage. By tucking the tail into a t-loop, the complex blocks the alarm signals (the ATM and ATR pathways) and prevents enzymes from "stitching" the ends of two chromosomes together. This prevents dangerous fusions and loss of genetic material.
Role in aging and disease
By regulating telomerase access, shelterin takes part in controlling telomere length. Mutations of its genes (for example, TINF2 or POT1) disrupt the protection of the ends and are linked to telomeropathies, as well as to a predisposition to certain tumours. A failure of the complex accelerates cellular senescence.
Calculate using this marker
Calculators where Shelterin is used directly:
Frequently asked questions
How does shelterin differ from telomerase?
Telomerase is the enzyme that rebuilds the telomere. Shelterin is the protective protein complex that shields the end of the chromosome and regulates when telomerase is allowed near it.
What happens if shelterin does not work?
The cell will perceive the ends of chromosomes as DNA breaks, trigger emergency repair and may "stitch" chromosomes together. This leads to genome instability, cellular senescence and disease.