Telomerase

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Telomerase

Structure of TERT from Tribolium castaneum

Telomerase is a ribonucleoprotein enzyme that adds nucleotide sequences to the ends of chromosomes, known as telomeres, thereby maintaining their length and stability. This enzyme is crucial for cellular aging and cancer biology.

Structure

Telomerase is composed of two main components: the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC). TERT is the catalytic subunit that acts as a reverse transcriptase, while TERC serves as a template for the addition of telomeric repeat sequences.

Illustration of telomerase structure and function

Function

Telomerase extends the 3' end of the DNA strand by adding repetitive nucleotide sequences, which compensates for the end replication problem that occurs during DNA replication. This activity is essential for the maintenance of genomic stability and is particularly active in stem cells, germ cells, and cancer cells.

Mechanism

Working principle of telomerase

The enzyme binds to the 3' end of the telomere and uses its RNA component as a template to synthesize DNA. This process involves the addition of the sequence "TTAGGG" in humans, which is repeated multiple times to extend the telomere.

Clinical Significance

Telomerase activity is tightly regulated in normal cells, but it is often upregulated in cancer cells, allowing them to divide indefinitely. This makes telomerase a target for cancer therapy.

Cancer

In most tumors, telomerase is reactivated, which contributes to the immortality of cancer cells. Inhibiting telomerase activity is a potential strategy for anticancer therapy.

Aging

Telomerase deficiency can lead to premature aging syndromes due to the progressive shortening of telomeres, which limits the replicative capacity of cells.

Therapeutic Approaches

Immunotherapy targeting telomerase

Telomerase Inhibitors

Research is ongoing to develop telomerase inhibitors that can selectively target cancer cells without affecting normal cells.

Immunotherapy

Immunotherapeutic approaches aim to target telomerase-expressing cells by stimulating the immune system to recognize and destroy these cells.

Antisense Oligonucleotides

Antisense oligonucleotides targeting telomerase

Antisense oligonucleotides can be designed to bind to the RNA component of telomerase, thereby inhibiting its activity.

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Contributors: Prab R. Tumpati, MD