negative regulation of telomere maintenance

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate or extent of a process that affects and monitors the activity of telomeric proteins and the length of telomeric DNA. [GOC:mah]

Negative regulation of telomere maintenance is a crucial biological process that controls the length and stability of telomeres, protective caps at the ends of chromosomes. Telomeres shorten with each cell division due to the "end replication problem", a phenomenon where DNA polymerase cannot fully replicate the ends of linear chromosomes. This shortening ultimately leads to cell senescence and apoptosis. To counteract telomere shortening, cells employ telomerase, an enzyme that adds DNA repeats to the ends of chromosomes. However, uncontrolled telomerase activity can lead to cancer, as it allows cells to bypass senescence and continue proliferating indefinitely. Therefore, precise regulation of telomere maintenance is essential for maintaining cellular homeostasis and preventing both premature aging and uncontrolled cell growth. Negative regulation of telomere maintenance involves various mechanisms that suppress telomerase activity or promote telomere shortening. These mechanisms include:

1. **Transcriptional regulation:** Transcription factors, such as TRF1 and TRF2, bind to telomeric DNA and suppress telomerase expression.
2. **Post-translational modifications:** Telomerase proteins can be modified by phosphorylation, ubiquitination, or sumoylation, affecting their activity or stability.
3. **Telomere-binding proteins:** Proteins like TIN2 and POT1 bind to telomeres and prevent telomerase access, inhibiting its activity.
4. **Alternative lengthening of telomeres (ALT):** This pathway, independent of telomerase, utilizes homologous recombination to maintain telomere length, but it is often associated with genomic instability.
5. **Senescence and apoptosis:** When telomeres reach a critically short length, cells enter senescence or undergo apoptosis, preventing uncontrolled proliferation.

These regulatory mechanisms ensure that telomere maintenance is tightly controlled, balancing telomere length preservation with the prevention of uncontrolled cell growth. Dysregulation of these mechanisms can contribute to aging, disease, and cancer development.'
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Proteins (2)

Compounds (2)