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Telomere Length

Telomeres are repetitive sequences of nucleotides (TTAGGG), which, along with specialized proteins, form a cap at the ends of chromosomes. They have various functions in preserving chromosome stability, protecting them from nucleolytic degradation, and preventing end-to-end fusion.

As telomeres progressively shorten, their protective function begins to decrease, resulting in fusion of sister chromatids and prolonged cycles characterized by breaks/fusions/bridges associated with many types of rearrangements typical of cancer cells. Significant telomere shortening can lead to telomeric dysfunction, which, in turn, may be directly implicated in chromosomal instability.

Telomere length depends on:

  1. telomerase activity, a ribonucleoprotein enzyme that elongates DNA;
  2. the shelterin complex (TERF1, TERF2, TIN2, hRAP1, TPP1, POT1), which influences telomere function by forming a protective cap against DNA degradation and inappropriate repair, preventing end fusion, and regulating telomerase activity;
  3. numerous telomere-associated proteins, including those involved in DNA repair and helicases.

In somatic cells, telomeres shorten with each cell division, leading to cellular senescence when they become critically short.

References

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