Telomérokat

Telomérokat are the protective caps at the ends of linear chromosomes in eukaryotic cells. They consist of repetitive nucleotide sequences bound by a set of specialized proteins, which together help prevent chromosome ends from being recognized as DNA breaks and from fusing with other chromosomes. In humans, telomeres are composed of TTAGGG repeats and can range from a few thousand base pairs to over ten kilobases, with length influenced by age, tissue type, and genetic factors.

Telomeres form a t-loop structure that hides the chromosome end from the DNA damage response. A six-protein complex known as shelterin binds telomeres and regulates their length and protection. Key components include TRF1, TRF2, POT1, TIN2, TPP1, and RAP1. The end-replication problem during DNA synthesis leads to progressive telomere shortening after each cell division, contributing to replicative senescence when critical length is reached.

Maintenance of telomeres is provided in germ cells, many stem cells, and most cancer cells by the enzyme telomerase, which adds TTAGGG repeats using an RNA template. In most somatic cells, telomerase activity is low or absent, so telomeres shorten with age. Some cells and tumors use an alternative lengthening of telomeres (ALT) mechanism, a recombination-based process, to maintain telomere length.

Telomere biology has implications for aging, tissue function, and cancer. Short telomeres are associated with cellular aging and age-related diseases, while excessively long telomeres can support cellular immortality in cancer. Methods to measure telomere length include terminal restriction fragment analysis, quantitative PCR, and fluorescence in situ hybridization.

Clinically, telomere biology disorders (telomeropathies) such as dyskeratosis congenita illustrate the consequences of defective telomere maintenance. Ongoing research explores telomerase modulation for cancer therapy and the broader impact of telomeres on health and longevity.