negative regulation of telomeric DNA binding

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of telomeric DNA binding. [GO_REF:0000059, GOC:BHF, GOC:BHF_telomere, GOC:nc, GOC:TermGenie, PMID:24415760]

Negative regulation of telomeric DNA binding is a crucial process in maintaining genome stability and preventing premature senescence. Telomeres, the protective caps at the ends of chromosomes, are composed of repetitive DNA sequences and associated proteins. They are essential for maintaining chromosome integrity during DNA replication. However, with each cell division, telomeres progressively shorten, leading to replicative senescence.

To counteract this shortening, cells employ a telomerase enzyme that adds back telomeric DNA sequences. However, dysregulation of telomerase activity can lead to uncontrolled cell proliferation and cancer.

Negative regulation of telomeric DNA binding involves a complex interplay of proteins and signaling pathways that control the activity of telomerase and other factors that interact with telomeric DNA. Key proteins involved in this process include:

- **TRF1 and TRF2:** These proteins bind to telomeric DNA and act as negative regulators of telomerase activity. They can inhibit telomerase by directly interacting with its components or by recruiting other factors that repress telomerase activity.
- **TIN2:** This protein bridges TRF1 and TRF2 with other proteins involved in telomere maintenance, including TPP1 and POT1.
- **TPP1:** This protein acts as a scaffold for the telomere-binding complex and recruits POT1.
- **POT1:** This protein binds to single-stranded telomeric DNA and protects it from degradation.

Negative regulation of telomeric DNA binding also involves post-translational modifications of these proteins, such as phosphorylation and ubiquitination. These modifications can alter their activity and interactions with other proteins.

In addition to these protein-mediated mechanisms, non-coding RNAs, such as TERRA, have also been implicated in the regulation of telomere length. TERRA interacts with telomeric DNA and can recruit proteins that influence telomere maintenance.

Ultimately, the negative regulation of telomeric DNA binding ensures that telomeres are maintained at appropriate lengths and that cells do not proliferate uncontrollably. Dysregulation of this process can have serious consequences for cellular function and organismal health.'
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Proteins (1)

Compounds (34)