Telomeres
Telomeres are the repetitive DNA–protein caps at chromosome ends: structures that protect coding DNA from the shortening of replication and that signal “chromosome end” so the cell treats them as a cap instead of a break.
Function
Human telomeres are several kilobases of TTAGGG repeats ending in a single-stranded overhang. The overhang folds back into the duplex, forming a t-loop that hides the chromosome end from the DNA damage machinery; the shelterin protein complex binds the repeats and represses the response that an exposed double-strand break would trigger (ATM, ATR). DNA polymerase cannot copy a linear template to its very end, so each S phase removes tens to hundreds of telomeric bases — the end-replication problem. Telomere length therefore tracks a cell’s replicative history, and critically short telomeres stop the cell through p53-mediated senescence.
In aging and cancer
Telomere shortening is the counting mechanism behind replicative senescence, and it makes telomeres a somatic lifespan clock: long-lived species tend to have longer telomeres and better telomere maintenance, and telomere length in blood cells correlates weakly with human mortality risk. Cancer requires escaping this clock, which tumors do by reactivating telomerase or the ALT recombination route. Dyskeratosis congenita, caused by telomerase mutations, presents the converse: short telomeres, premature aging phenotypes, and bone-marrow failure.
Notes
- Shelterin components: TRF1, TRF2, POT1, TPP1, TIN2, RAP1.
- Elizabeth Blackburn and Jack Szostak discovered telomere maintenance; the 2009 Nobel Prize recognized the work.
- The finite division limit that telomere shortening explains was established by the Hayflick–Moorhead experiment.