6.12: Telomeres and Telomerase
In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded DNA. To avoid this, a buffer zone composed of a repeating nucleotide sequence and a protein complex, called a telomere is present at the ends of the chromosomes which protects the ends of the chromosomes.
Telomerase, a ribonucleoprotein enzyme composed of both RNA and proteins, can synthesize and elongate the lost DNA. Telomerase RNA component (TERC) contains a template nucleotide sequence for the synthesis of the telomeric repeats. The TERC length and sequence vary between organisms In ciliates, it is around 150 nucleotides long, whereas, in yeast, it is approximately 1150 nucleotides. The protein component, telomerase reverse transcriptase (TERT), synthesizes short telomere repeats using the template strand present in the TERC.
In mammals, the telomere is protected by shelterin which is a complex of six different proteins: telomeric repeat binding factor 1 (TRF1), telomeric repeat binding factor 2 (TRF2), protection of telomere 1 (POT1), TRF1 interacting nuclear factor 2 (TIN2), TIN2-POT1 organizing protein (TPP1) and repressor/activator protein 1 (RAP1). Proteins present in the shelterin complex are involved in important functions such as telomerase recruitment, regulation of telomere length, and providing binding sites for accessory proteins.
Telomerase expression can increase the lifespan of a cell and allow it to proliferate continuously, a characteristic feature of a cancer cell. Telomerase activity has been observed in almost 90% of cancer cells which makes them a target of current research for new cancer treatments.