Telomerase – Structure, Mechanism, Regulation, Functions

What is Telomerase?

Telomerase (terminal transferase) is a ribonucleoprotein enzyme that extends telomeres, the repetitive nucleotide sequences at the ends of eukaryotic chromosomes. Telomeres function as protective caps, stopping chromosome ends from being erroneously perceived as DNA damage or from bonding with neighboring chromosomes. Most eukaryotes use telomerase to maintain their telomeres, but some organisms, including Drosophila melanogaster, use retrotransposons to do so.

This enzyme works as a reverse transcriptase and adds telomeres by using its own RNA template. For instance, in Trypanosoma brucei, telomerase template is an RNA sequence (3′-CCCAAUCCC-5′). Telomerase activity is high in gametes and many cancer types whereas it is repressed in somatic cells. The discovery had been preceded by Soviet biologist Alexey Olovnikov’s 1973 observation of a shortening mechanism of telomeres, which he speculated as a compensatory function with relevance to aging, cancer and neurodegenerative diseases.

Telomerase was first discovered in the ciliate Tetrahymena by Carol W. Greider and Elizabeth Blackburn in 1984 — a breakthrough that earned them and Jack W. Szostak the Nobel Prize in Physiology or Medicine in 2009. Breakthroughs in structural biology provided cryo-electron microscopy (cryo-EM) structures of telomerase, first from Tetrahymena thermophila and then from human cells. These studies also helped to understand the molecular architecture of the enzyme, which in turn provided insight into its function and regulation.

The work of scientists at Geron Corporation cloning human telomerase RNA and catalytic subunits has further underscored the enzyme’s role in aging and cancer. Also, they took an effort to develop the TRAP assay, a PB-PCR based method for detection of telomerase activity, especially in the case of cancer cells. This was the first time a scientific innova­tion made it possible to study how telomerase, or a loss of telomeres, leads to cellular immortality, a characteristic of cancer.

In 2018, UC Berkeley scientists were able to use cryo-EM to resolve the human telomerase structure, providing insight into both the complexity of the enzyme and its potential as a therapeutic target. These findings are deepening our understanding of telomere biology and its potential role in medicine, particularly in the field of aging and oncology.

Telomerase Definition

Telomerase is a ribonucleoprotein enzyme that maintains the protective telomere sequences at the ends of eukaryotic chromosomes by adding repetitive nucleotide sequences, ensuring chromosome stability and preventing DNA degradation.

Telomerase Structure

It’s a ribonucleoprotein complex that protects eukaryotic chromosomes from damage. It ensures that telomeres remain the correct length and does so by attaching new copies (telomerics) onto the ends when they shorten after every division of the cell.

The structure is organized and combined with each subunit playing a different role in its function.

Below is an overview of the structure of telomerase.

• Core Components:
  • Telomerase Reverse Transcriptase (TERT):
    • Catalytic subunit.
    • contains 4 conserved domains.
    • Rna-binding domain, fingers, palm, thumb.
    • Right-handed construction.
    • Such a structure enables TERT to function as a reverse transcriptase, transcribing RNA to produce DNA.
  • Telomerase RNA Component (TERC):
    • A non-coding RNA serving as template for telomere extension.
    • Direct interaction with TERT guides the addition of telomeric repeats to chromosome ends.
  • Dyskerin (DKC1):
    • Stabilizes the complex and ensures correct folding of TERC.
• Accessory Subunits:
  • Telomere-associated proteins like TRF1, TRF2, TPP1, POT1, TIN2 and RAP1 (together known as the shelterin complex) interface with telomerase to regulate telomere length and structure.
  • TRF1 and TRF2 keep telomerase from doing its work by inhibiting the activity of the enzyme.
  • Instead, they allow telomeric extensions to be carried out in a controlled manner through vonaplate9’
  • POT1 protects the end of telomeres, which is single-stranded and easily joined or degraded.
• Telomerase Gene Locations in Humans:
  • TERT: Encodes the catalytic subunit and is located on chromosome 5.
  • TERC: Encodes the RNA template and is located on chromosome 3.
  • Others such as DKC1 and TEP1 have their own separate coding genes.
• Structural Adaptations:
  • The TERT subunit incorporates a “glove” area for everything to be wrapped into place, including telomeres, making sure that only one single-stranded telomere sequence is tacked on.
  • This elaborate configuration draws upon elements from the reverse transcriptases of retroviruses as well as the polymerases of other polymerases, testifying to conservation during evolution.
• Function in Tissues and Development:
  • The activity of telomerase is strictly regulated. It is abundant in embryonic cells and tissues with high proliferation potential and reduced in most somatic cells.
  • Disruption to these components can lead progressive telomeric shortening or lengthening and thus aging; also into cancer cardiovascular conditions.

Telomere-Binding Proteins

Telomere-binding proteins play critical roles in maintaining the integrity of telomeres, regulating telomere length, and controlling telomere-related functions like gene silencing. These proteins interact with telomeric DNA to form protective structures, which are essential for cellular stability.

• Telomere DNA Structure:
  • In yeast, telomeres consist of a double-stranded region (250-350 bp) with a C1-3A/TG1-3 sequence and a single-stranded protruding end with a TG1-3 sequence. This structure contrasts with mammalian telomeres, which have homogeneous TTAGGG repeats.
  • Yeast telomeres contain both double-stranded and single-stranded regions, each interacting with different proteins to regulate telomere length and maintain telomere function.
• Proteins in Yeast:
  • Rap1p binds directly to the double-stranded region of yeast telomeres and interacts with silent information regulator (Sir) proteins, which contribute to heterochromatin formation. Rap1p also associates with Rif1p and Rif2p, negative regulators of telomerase activity.
  • Cdc13p binds to the single-stranded region of yeast telomeres and regulates telomerase access. It can interact with two protein complexes: one promoting telomere elongation (via Est1p) and another inhibiting elongation (via Stn1p–Ten1p complex).
  • Ku proteins interact at the junction of single- and double-stranded telomere regions, where they protect telomeres and participate in telomerase binding during the G1 phase of the cell cycle.
• Proteins in Mammals:
  • TRF1 and TRF2 bind the double-stranded region of mammalian telomeres, while POT1 and TPP1 bind the single-stranded region.
  • The interaction between these proteins is mediated by the TIN2 protein, which links TRF1, TRF2, and TPP1. This assembly of proteins is known as shelterin, a complex that protects telomeres and regulates telomere length.
• Telomere-Binding Proteins in Other Organisms:
  • In S. pombe, the telomere-binding protein Taz1p binds double-stranded telomeric DNA instead of Rap1p. Pot1p binds the single-stranded region, similar to mammalian POT1.
  • In ciliates, TEBPα and TEBPβ bind the 3′-protruding end of telomeres. These proteins are orthologous to POT1 and TPP1 in mammals, highlighting a conserved mechanism across species.
• G-Quadruplexes and Telomeres:
  • The 3′-end of telomeric DNA can form G-quadruplexes, which are structures formed by guanine-rich sequences that can hinder DNA replication and telomere elongation by telomerase.
  • POT1 in mammals prevents the formation of these G-quadruplexes, allowing telomerase to elongate telomeres. The position of POT1 relative to the 3′-end is crucial for its function in promoting telomere elongation.
• Telomeric RNA (TERRA):
  • In various species, including S. cerevisiae, human, and mouse cells, polymerase II transcribes telomeric repeats, generating TERRA (Telomere Repeat-Containing RNA).
  • TERRA is associated with telomeric chromatin, and its levels correlate with telomere dysfunction. In yeast, TERRA inhibits telomerase, while in humans, increased TERRA levels are associated with telomere loss and potential oncogenesis.
• Telomere Localization:
  • In yeast, telomeres cluster at the nuclear membrane, a localization that may be vital for telomere replication and the assembly of the telomere-protein complex post-replication.

Mechanism of Telomere Elongation by Telomerase

Telomere elongation is a crucial process in maintaining chromosome stability. Telomerase is an enzyme that extends the telomeric ends of chromosomes, counteracting the shortening that occurs during DNA replication. This process involves a series of coordinated steps, where both the telomerase enzyme and various telomere-associated proteins play key roles.

1. Primer Binding
   • Telomerase begins by binding to the 3′ end of a telomere, which features a single-stranded overhang.
   • This binding is driven by interactions between the telomerase RNA component (TER) and the DNA primer.
   • The “anchor site” within TER stabilizes the enzyme-DNA complex, setting the stage for elongation.
2. Elongation
   • Once bound, telomerase uses its reverse transcriptase activity to add nucleotides to the primer.
   • The RNA template in TER guides the synthesis of guanine-rich telomeric repeats, such as TTAGGG in humans.
   • Multiple nucleotide additions can occur in a single binding event, extending the telomere.
3. Translocation
   • After each nucleotide addition, telomerase translocates along the DNA primer to continue elongation.
   • Translocation I: The RNA-DNA duplex moves relative to the enzyme, allowing for continuous elongation of the telomere.
   • Translocation II: Telomerase shifts its position along the DNA after adding a single repeat, without fully dissociating, enabling further extension of the telomere.
4. Dissociation
   • After several repeats are added, telomerase may dissociate from the DNA primer.
   • Dissociation can be temporary, allowing the enzyme to rebind and continue elongation or, depending on cellular conditions, it may release completely.
   • This step is regulated by various mechanisms within the cell, determining whether telomerase remains active or is removed.

How Telomerase Overcomes the End-Replication Problem

The end-replication problem refers to the inability of conventional DNA polymerases to fully replicate the ends of linear chromosomes, which leads to progressive shortening of telomeres with each cell division. Telomerase solves this issue by extending the telomeres, allowing for continued cell division without losing critical genetic information.

• Telomeric Repeat Addition
  • Telomerase adds telomeric repeats (e.g., TTAGGG in humans) to the 3′ ends of chromosomes.
  • The RNA component of telomerase serves as a template for these repeats, compensating for the incomplete replication caused by DNA polymerases.
  • This process ensures that the telomere length is maintained even after each round of replication.
• Template-Driven Elongation
  • The RNA template in telomerase is complementary to the telomeric repeat sequence.
  • Telomerase binds to the single-stranded overhang of the chromosome and uses its RNA template to extend the telomere by adding G-rich repeats.
  • This mechanism ensures that the telomeres are elongated, providing a stable template for further DNA replication.
• Formation of T-Loops
  • Telomeres can form T-loops, where the single-stranded overhang folds back into the double-stranded telomere region.
  • This looped structure protects telomere ends from being mistaken as DNA breaks by the cell’s repair machinery.
  • By shielding telomere ends from repair processes, T-loops prevent chromosome fusion or degradation.
• Recruitment and Regulation of Telomerase
  • Telomerase activity is regulated based on the cell cycle, primarily active during the S phase.
  • Shelterin proteins, such as TPP1, help recruit telomerase to the telomeres, ensuring proper elongation when necessary.
  • Other protein complexes can suppress telomerase activity when it’s not needed, maintaining genomic stability and preventing excessive elongation.
• Collaboration with DNA Replication Machinery
  • Telomerase extends the 3′ end of the telomere, creating a longer template for DNA polymerases.
  • This provides the necessary template for the replication of both telomeric strands.
  • By aiding in the replication of both strands, telomerase ensures that chromosome integrity is preserved through multiple rounds of cell division.

Activation of Telomerase

Telomerase activity is essential for telomere length maintenance and is associated with aging and cancer progression. Molecules and mechanisms that stimulate telomerase activation have been described; such activators are promising therapeutic options for areas such as anti-aging and regenerative medicine.

• Low Molecular Weight Activators
  • A growing body of research focuses on the in vivo design of low molecular weight compounds that interact directly with telomerase to enhance enzyme function.
  • These compounds work to reactivate endogenous telomerase, potentially restoring telomere length in tissues where it may be beneficial therapeutically.
  • The trick, though, is keeping telomerase activity around in the tissues where it’s needed.
• Activation in Specific Cell Types
  • A good target for telomerase activation is stem Cells in regenerating tissues, as they have moderate telomerase activity by default.
  • These activators may be useful for lymphocytes that also have low telomerase activity to sustain or regain their proliferative capacity.
  • These approaches have been investigated to help stimulate immune activity or to help renovate aged tissues.
• Cycloastragenol and Its Derivatives
  • Cycloastragenol, a compound from the traditional medicinal plant Astragalus membranaceus, is among the most promising telomere activators.
  • The TAT2 cycloastragenol derivative has raised profile in vivo activity in feline studies and idiopathic pulmonary fibrosis models.
  • These inhibitors are considered potential candidates for telomerase-targeted therapies that transiently activate telomerase in selected tissues.
• TA-65 Activation
  • TA-65, a different activator derived from Astragalus, has been studied in clinical programs geared toward health maintenance.
  • TA-65 induces telomerase activity in human keratinocytes, fibroblasts and immune cells at low nanomolar concentrations.
  • It is associated with improvements in biomarkers of aging like cardiovascular health, metabolism and bone density.
• Oxidative Stress and ROS Mitochondrial Dysfunction
  • Telomere-dependent aging is largely driven by mitochondrial dysfunction and generation of reactive oxygen species (ROS), leading to telomere-shortening (both by oxidative stress) and senescence.
  • Antioxidants can alleviate some of the effects of ROS, thus delaying vascular aging and decreasing deposition of cellular damage.
  • As a result, there are in vitro studies show that antioxidant species like N-acetylcysteine may protect telomerase activity by preventing the export of hTERT from the nucleus and thereby avoiding premature senescence 36.
• Extracts from Natural Sources
  • Ginkgo biloba extracts, for example, are natural compounds that have been shown to activate telomerase.
  • Such extracts act through activation of the PI3K/Akt signaling pathway which is essential for telomerase activation.
  • Yet, PI3K inhibition markedly hampers the effects of Ginkgo biloba, indicating that this pathway is likely a key component in the mechanism of Ginkgo biloba.

Mechanisms of Telomerase Inhibition

Telomerase inhibition is a promising approach in cancer therapy, particularly for targeting cells with high telomerase activity. The mechanisms of inhibiting telomerase involve various strategies aimed at disrupting its activity, targeting its components, or interfering with its associated proteins. Below are the key mechanisms of telomerase inhibition.

• Direct Inhibition of TERT
  • The telomerase reverse transcriptase (TERT) subunit is the catalytic component responsible for adding telomeric repeats to the chromosome ends.
  • Small molecules like BIBR1532 are non-nucleosidic inhibitors that bind directly to TERT, inhibiting its catalytic function.
  • By blocking the enzyme’s processivity, these compounds prevent the elongation of telomeres during DNA synthesis.
• Targeting the RNA Component (TR)
  • The telomerase RNA component (TR) plays a crucial role in guiding TERT to the telomeres.
  • Imetelstat (GRN163L), a synthetic oligonucleotide, specifically binds to TR, thereby inhibiting its function.
  • This approach has been explored in various cancers, such as myelofibrosis and thrombocytopenia, to suppress telomerase activity.
• Modified Deoxynucleoside Triphosphates (dNTPs)
  • Some modified deoxynucleoside triphosphates (dNTPs) can interfere with telomerase activity.
  • Oxidized dNTPs, such as ddITP and AZT-TP, act as chain terminators when incorporated into the DNA strand, effectively halting telomere elongation by preventing further nucleotide addition.
  • Other modified dNTPs, like 6-thio-dGTP, inhibit telomerase by disrupting translocation, preventing the enzyme from moving along the DNA strand after nucleotide addition.
• Antisense Oligonucleotides and RNA Interference
  • Antisense oligonucleotides or small interfering RNA (siRNA) are techniques that reduce TERT expression at the transcriptional level.
  • These synthetic nucleic acids bind to specific mRNA targets, leading to decreased production of the TERT protein, which is necessary for telomerase function.
• Natural Products
  • Natural compounds derived from plants have also been identified as telomerase inhibitors.
  • These include polyphenols and terpenoids, which can destabilize telomeres or directly inhibit telomerase activity.
• Inhibition of Associated Proteins
  • Another strategy involves targeting proteins associated with telomerase, such as tankyrases, which regulate telomere length.
  • Disrupting these protein interactions can lead to indirect inhibition of telomerase, reducing its overall activity and contributing to telomere shortening.

Examples of Telomerase Inhibitors

Telomerase inhibitors are gaining attention as potential cancer treatments due to their ability to target the enzyme responsible for maintaining telomere length in cancer cells. Several compounds have been identified as telomerase inhibitors, each utilizing different mechanisms to suppress telomerase activity. Below are some notable examples.

• BIBR1532
  • BIBR1532 is a non-nucleosidic compound that targets the core components of telomerase.
  • It acts as a mixed-type non-competitive inhibitor, reducing the number of telomeric repeats added during DNA synthesis.
  • In various cancer cell lines, BIBR1532 has shown cytotoxic effects, particularly in hematopoietic cancer cells.
• GRN163L (Imetelstat)
  • GRN163L is a synthetic oligonucleotide that binds to the RNA component of telomerase, blocking its function.
  • It has demonstrated a competitive inhibition profile with an IC50 ranging from 0.5–10 nM.
  • GRN163L has entered clinical trials for chronic lymphocytic leukemia (CLL) and advanced solid tumors.
• AZT (3′-azido-2′,3′-dideoxythymidine)
  • Originally used as an antiviral drug, AZT has been found to inhibit telomerase activity and shorten telomeres in cancer cells.
  • AZT can also enhance the effects of other chemotherapeutic agents like cisplatin and paclitaxel, making it a potential adjunct therapy in cancer treatment.
• MST-199 and MST-312
  • These are synthetic compounds specifically designed to inhibit telomerase activity.
  • MST-199 has shown promise in targeting various cancers by disrupting telomerase function.
  • MST-312 is noted for its ability to downregulate telomerase activity effectively.
• Silibinin
  • Silibinin, a polyphenolic flavonoid, has been shown to downregulate telomerase activity in prostate cancer cells.
  • It also reduces prostate-specific antigen (PSA) levels and can be combined with other compounds like curcuminoids to enhance its inhibitory effects on telomerase.
• Telomestatin
  • Telomestatin is a natural product isolated from Streptomyces anulatus.
  • It inhibits telomerase activity and has been shown to enhance the effectiveness of traditional chemotherapeutic agents when used in combination therapies.
• Peptide Nucleic Acids (PNAs)
  • PNAs are synthetic polymers that bind specifically to the RNA component of telomerase.
  • This binding inhibits telomerase activity and reduces the proliferation of cancer cells.

Methods Used for Measurement of Telomere Length (TL)

Measuring telomere length (TL) is essential for understanding telomere biology and its relationship to aging, cancer, and various diseases. Several techniques have been developed over time, each with its own advantages and limitations. Here are the primary methods used for measuring TL.

• Telomere Restriction Fragment (TRF) Analysis
  • Method: Involves Southern blot hybridization using probes against telomere repeats.
  • Advantages: This widely-used technique doesn’t require special reagents or equipment.
  • Limitations: Quantification is challenging, and it requires a large number of cells (~1 million). This method provides an estimate of the average telomere length and can be affected by subtelomeric polymorphisms.
• qPCR (Quantitative PCR)
  • Method: Developed by RM Cawthon in 2002, qPCR measures telomeric DNA with fluorescent signals using partially mismatched primers. The T/S ratio (telomere-to-single-copy gene ratio) is used to estimate relative telomere length.
  • Advantages: Requires a small amount of DNA (20 ng) and can measure TL quickly, making it ideal for large-scale epidemiological studies.
  • Limitations: There is a wide range of variability (2-28%) in TL measurements, making repeatability an issue. Proper optimization of qPCR conditions is necessary to reduce variability.
• Monochrome Multiplex qPCR (MMqPCR)
  • Method: An improved version of qPCR, MMqPCR amplifies both telomeric DNA and a single-copy gene in the same well.
  • Advantages: Has less variability compared to monoplex qPCR and requires fewer samples.
  • Limitations: Like qPCR, MMqPCR requires careful optimization to minimize experimental variability.
• Flow-FISH (Fluorescence In Situ Hybridization) Assay
  • Method: This assay uses fluorescent peptide nucleic acid (PNA) oligonucleotide probes to specifically label telomeres.
  • Advantages: Provides high sensitivity and specificity, with the ability to measure TL at the single-cell level.
  • Limitations: Requires expensive equipment and cannot assess TL in tissues or stored samples. It is also limited to cells in the replicating stage (metaphase), making it less suitable for interphase cells.
• Single Telomere Length Analysis (STELA)
  • Method: A ligation PCR-based method that measures the length of individual telomeres.
  • Advantages: Does not require specialized equipment and uses very limited starting material.
  • Limitations: The method is labor-intensive and not suitable for large sample sizes.

How Does Telomerase Activity Influence Cellular Aging?

Telomerase activity plays a crucial role in determining how cells age, primarily by affecting the length of telomeres and influencing cellular division potential. Its activity can delay or accelerate aging processes, depending on the context.

• Telomere Length Maintenance
  • Telomerase counters the natural shortening of telomeres that happens during DNA replication.
  • In somatic cells, telomerase is typically inactive, causing telomeres to shorten with every cell division.
  • As telomeres shorten, cells eventually enter a state of senescence, limiting their ability to continue dividing.
• Cellular Senescence
  • When telomeres become critically short, they signal the cell to enter senescence.
  • This is a protective mechanism to prevent uncontrolled cell division and tumor formation.
  • However, the downside is that senescent cells lose their ability to divide, reducing the overall pool of functional cells and contributing to aging at the tissue level.
• Regulation of Cell Division Potential
  • Somatic cells are bound by the Hayflick limit, which restricts the number of times a cell can divide.
  • This limit occurs because of the progressive shortening of telomeres.
  • Stem cells and germ cells, however, have active telomerase and can maintain telomere length, allowing for indefinite cell division.
• Role in Cancer
  • In cancer cells, telomerase is often reactivated, which enables these cells to bypass the normal limitations on cell division.
  • This reactivation promotes the immortality of cancer cells, driving tumor growth and progression.
  • While telomerase is essential for normal tissue regeneration, its unchecked activity in cancer cells can contribute to accelerated aging at the organism level by increasing cancer risk.
• Potential for Therapeutic Intervention
  • Telomerase is a target for therapeutic strategies aimed at aging and cancer.
  • Inhibiting telomerase activity is being explored as a way to treat cancers by limiting the proliferative ability of tumor cells.
  • On the flip side, activating telomerase could hold potential for therapies targeting age-related diseases, as it could promote tissue regeneration by allowing cells to divide and repair damaged tissues more effectively.

What Are the Regulatory Mechanisms of Telomerase Activity?

Telomerase activity is tightly controlled through several regulatory mechanisms that ensure its proper function under specific conditions and in various cell types.

• Cell Cycle Regulation
  • Telomerase is most active during the S phase of the cell cycle when DNA replication takes place.
  • Regulatory proteins ensure that telomerase is activated only at the right time, enabling it to elongate telomeres during DNA synthesis.
• Expression of Telomerase Components
  • The telomerase reverse transcriptase (TERT) and telomerase RNA component (TER) expression levels are tightly regulated.
  • In somatic cells, TERT expression is low or absent, limiting telomerase activity.
  • In contrast, stem cells, germ cells, and many cancer cells express high levels of TERT, leading to active telomerase.
• Post-Translational Modifications
  • Telomerase activity can be influenced by post-translational modifications of TERT, such as phosphorylation and acetylation.
  • These modifications can enhance TERT’s activity or alter its stability and localization, ensuring that it functions properly during telomere maintenance.
• Binding of Accessory Proteins
  • Auxiliary factors help assemble and stabilize the telomerase complex.
  • Proteins like shelterin, particularly TPP1, play a crucial role in recruiting telomerase to telomeres and regulating its function, ensuring telomerase interacts effectively with its target sites.
• Regulatory RNA Molecules
  • TERRA, a telomeric repeat-containing RNA, is produced from telomeres and can influence telomerase activity.
  • TERRA interacts with telomerase components and modulates their function, adding another layer of regulation in maintaining telomere length.
• Feedback Mechanisms
  • Cells are capable of sensing their telomere length.
  • When telomeres become critically short, signaling pathways are triggered that either inhibit telomerase activity or induce senescence.
  • This feedback mechanism ensures the stability of the genome by preventing excessive elongation or further shortening of already critically short telomeres.
• Inhibition by Telomerase Inhibitors
  • Natural compounds and synthetic drugs can inhibit telomerase activity.
  • These inhibitors may target TERT directly or interfere with its interaction with RNA or accessory proteins, making them potential tools in cancer therapy by limiting the proliferation of cancer cells.

Functions of Telomerase

Telomerase serves several essential functions that contribute to maintaining the stability of the genome and promoting cellular longevity. These functions go beyond merely elongating telomeres and are critical for processes like cellular proliferation, aging, and disease.

• Telomere Length Maintenance
  • Telomerase adds guanine-rich repetitive sequences to the ends of chromosomes.
  • This action counteracts the natural shortening of telomeres that occurs during DNA replication.
  • Since conventional DNA polymerases cannot fully replicate the ends of linear chromosomes, telomerase is essential to prevent gradual telomere attrition with each cell division.
• Prevention of Chromosome Degradation
  • By elongating telomeres, telomerase protects chromosome ends from degradation by nucleases and other damaging factors.
  • This protection is crucial for preserving genome integrity and avoiding chromosomal fusion, which can lead to genomic instability.
• Facilitation of Cellular Proliferation
  • Telomerase activity allows certain cells, like stem and germ cells, to divide indefinitely.
  • This is vital for processes such as growth, tissue regeneration, and repair.
  • In contrast, somatic cells, which lack telomerase activity, reach a limit on their replicative potential due to telomere shortening, leading to senescence.
• Role in Cancer Biology
  • In roughly 85% of cancer cells, telomerase is reactivated.
  • This reactivation allows cancer cells to bypass normal aging mechanisms and continue proliferating without limit.
  • The persistence of telomerase activity in tumors is linked to cancer progression, making it an attractive target for therapeutic interventions.
• Regulation of the Cell Cycle
  • Beyond telomere elongation, telomerase may also play a role in regulating the cell cycle.
  • Its activity can influence how cells respond to stress or DNA damage, which in turn affects their survival and proliferation.
• Potential Role in Aging and Disease
  • Telomere shortening is associated with cellular senescence and age-related diseases.
  • Studying telomerase’s functions may reveal insights into aging processes and provide potential avenues for therapeutic strategies aimed at extending cell lifespan or mitigating age-related conditions.