Telomeres are specialized structures found at the ends of linear chromosomes in eukaryotic cells. They consist of repetitive DNA sequences and associated proteins that protect the chromosome ends from degradation, fusion, and recognition as damaged DNA. In humans, the telomeric DNA sequence is made up of thousands of repeats of the nucleotide sequence TTAGGG.
Telomeres play several essential roles in cellular function:
- Chromosome stability: Telomeres protect the ends of chromosomes, preventing them from being recognized as broken DNA and preventing unwanted chromosome fusions or rearrangements.
- Replicative senescence: Telomeres shorten with each cell division due to the end-replication problem, which occurs because DNA polymerase cannot fully replicate the ends of linear DNA molecules. When telomeres become critically short, cells enter a state of replicative senescence, which means they cease dividing and may undergo apoptosis (programmed cell death) or become senescent. This process limits the number of times a cell can divide, acting as a molecular “clock” and contributing to cellular aging.
- Genome integrity: By creating a buffer of non-coding, repetitive DNA sequences, telomeres help preserve essential genetic information during replication, ensuring that important coding regions are not lost.
Telomerase, a specialized enzyme, can add telomeric repeats to the chromosome ends, counteracting telomere shortening. In most human somatic cells, telomerase activity is low or absent, resulting in progressive telomere shortening and eventual cellular senescence. However, certain cells, such as stem cells, germ cells, and some immune cells, have active telomerase to maintain their telomeres and ensure their long-term functionality.
In the context of cancer, telomerase is reactivated in approximately 85-90% of human tumors, allowing cancer cells to maintain or even elongate their telomeres and providing them with unlimited replicative potential. This characteristic has made telomerase an attractive target for cancer therapy, and numerous strategies to inhibit telomerase activity are being investigated.
Understanding telomere biology and the factors that influence telomere maintenance is crucial for advancing our knowledge of cellular aging, age-related diseases, and cancer.