TTAGGG

TTAGGG is the hexanucleotide DNA sequence that forms the core repeat unit of telomeres, the protective caps at the ends of linear chromosomes in most vertebrates, including humans. This sequence is tandemly repeated thousands of times, with the G-rich strand extending as a 3' overhang that is key to telomere function.

Telomeres protect chromosome ends from degradation, end-to-end fusions, and inappropriate activation of DNA damage responses during replication. Each cell division shortens telomeres due to the end-replication problem, unless the repeats are replenished. In humans and other vertebrates, the enzyme telomerase adds TTAGGG repeats to the 3' end, using an RNA template. Telomerase activity is high in germ cells and many stem cells, low in most somatic cells, and often reactivated in cancer cells.

Telomeres are protected by the shelterin protein complex, which specifically recognizes TTAGGG repeats. Shelterin components include TRF1 and TRF2 (which bind double-stranded telomeric DNA), POT1 (which binds the single-stranded 3' overhang), and TIN2, TPP1, and RAP1 that connect these interactions and regulate access to the telomere.

Telomere length and composition vary by tissue and species. Some organisms employ alternative lengthening of telomeres (ALT), a recombination-based mechanism, to maintain telomeres in the absence of telomerase.

TTAGGG repeats and telomere biology are central to aging, cancer, and development. The discovery of telomerase and its action on TTAGGG repeats earned Elizabeth Blackburn, Carol Greider, and Jack Szostak the Nobel Prize in Physiology or Medicine in 2009.