telomere maintenance via telomere lengthening

Definition

Target type: biologicalprocess

Any process that contributes to the maintenance of proper telomeric length and structure by affecting and monitoring the activity of telomeric proteins and lengthening the telomeric DNA. [GOC:dph, GOC:tb]

Telomere maintenance via telomere lengthening is a critical process that ensures the stability and integrity of chromosomes during cell division. Telomeres are protective caps at the ends of chromosomes, preventing DNA degradation and fusion. However, with each round of replication, telomeres naturally shorten due to the end-replication problem, where DNA polymerase cannot fully replicate the 3' end of the lagging strand. This shortening can lead to genomic instability and cellular senescence.

To counter this, cells have evolved mechanisms to lengthen telomeres. The primary pathway involves the enzyme telomerase, a reverse transcriptase that adds repetitive DNA sequences (TTAGGG) to the ends of chromosomes. Telomerase contains two key components: a catalytic subunit (TERT) and a template RNA component (TERC). TERC provides the template for synthesizing the TTAGGG repeats, while TERT has the enzymatic activity to add these repeats to the telomere.

The process of telomere lengthening by telomerase can be summarized as follows:

1. Telomerase binds to the telomere, recognizing the single-stranded 3' overhang.
2. The TERC RNA component within telomerase acts as a template for synthesizing new DNA sequences.
3. TERT, the catalytic subunit, uses the template to add TTAGGG repeats to the 3' end of the lagging strand.
4. This extension of the telomere counteracts the shortening that occurs during replication.

Telomerase activity is tightly regulated in most somatic cells, with low or undetectable levels. However, in germ cells and stem cells, telomerase is highly active, ensuring the maintenance of telomere length throughout generations. Additionally, some cancer cells reactivate telomerase to sustain their uncontrolled proliferation.

While telomerase is the primary pathway for telomere lengthening, alternative mechanisms also exist. These include homologous recombination (HR) and alternative lengthening of telomeres (ALT). HR utilizes homologous sequences on sister chromatids to repair telomere breaks and extend the ends. ALT is a more complex process that involves recombination between telomeric repeats and other DNA sequences, resulting in telomere lengthening.

In summary, telomere maintenance via telomere lengthening is essential for maintaining genomic integrity and cell viability. Telomerase plays a key role in this process by adding repetitive DNA sequences to the ends of chromosomes, counteracting the natural shortening that occurs during replication. The regulation of telomerase activity and the existence of alternative lengthening pathways contribute to the complex and multifaceted nature of telomere maintenance.'
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Proteins (1)

Compounds (4)