regulation of telomere maintenance via telomerase

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of the addition of telomeric repeats by telomerase. [GOC:mah]

Telomere maintenance is a critical process for maintaining genomic integrity and cellular lifespan. Telomeres, the protective caps at the ends of chromosomes, shorten with each cell division due to the end replication problem. This shortening can lead to genomic instability and cellular senescence. To counter this, cells employ a specialized enzyme called telomerase, which adds DNA repeats to the telomere ends. Telomerase is a ribonucleoprotein complex consisting of a catalytic subunit (TERT) and a template RNA subunit (TERC). TERT possesses reverse transcriptase activity, using TERC as a template to synthesize DNA repeats. The regulation of telomerase activity is tightly controlled, ensuring proper telomere maintenance while preventing uncontrolled cell proliferation.

Several factors regulate telomerase activity, including:

**Transcriptional Regulation:** The expression of TERT and TERC genes is tightly controlled. Transcription factors, such as MYC, E2F1, and NF-κB, can activate TERT transcription, while factors like p53 and Rb can repress it. This regulation ensures that telomerase is only active in cells that need it, such as stem cells and germ cells.

**Post-translational Modification:** TERT can undergo various post-translational modifications, such as phosphorylation, acetylation, and ubiquitination, which can modulate its activity and stability. These modifications can be influenced by signaling pathways activated by growth factors, hormones, and stress.

**Subcellular Localization:** Telomerase is localized to the nucleus, where it interacts with telomeres. However, its localization can be regulated by factors like cell cycle progression and the presence of specific protein partners.

**Telomere Binding Proteins:** Several proteins bind to telomeres and regulate telomerase access. These proteins, such as TRF1, TRF2, and POT1, can promote or inhibit telomerase activity based on telomere length and other factors.

**Cellular Context:** The regulation of telomerase activity is also influenced by the cellular context. For example, stem cells require high telomerase activity to maintain their proliferative capacity, while differentiated cells typically have low or no telomerase activity.

Dysregulation of telomerase activity can lead to various diseases, including cancer and premature aging. Overexpression of telomerase is often observed in cancer cells, allowing them to proliferate indefinitely. Conversely, mutations in telomerase genes can cause accelerated telomere shortening and premature aging.

In summary, telomerase regulation is a complex process involving multiple levels of control, ensuring that telomeres are properly maintained while preventing uncontrolled cell proliferation. Understanding the intricate mechanisms regulating telomerase activity is crucial for developing therapeutic strategies to address telomere-related diseases.'
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Proteins (3)

Compounds (55)