positive regulation of telomere maintenance
Definition
Target type: biologicalprocess
Any process that activates or increases 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]
Positive regulation of telomere maintenance is a crucial cellular process that ensures the stability and integrity of chromosomes, preventing genomic instability and cellular senescence. Telomeres are protective caps at the ends of chromosomes that prevent degradation and fusion. During DNA replication, telomeres shorten with each round of cell division, eventually leading to cellular senescence if left unchecked. The process of positive regulation of telomere maintenance aims to counter this shortening and maintain telomere length, allowing cells to continue dividing and survive.
This regulation involves a complex interplay of factors, including:
1. **Telomerase:** This enzyme, a specialized reverse transcriptase, adds DNA repeats (TTAGGG) to the ends of telomeres, compensating for the loss that occurs during replication. Telomerase activity is tightly regulated, with high levels in germ cells and stem cells, but low or absent levels in most somatic cells.
2. **Shelterin Complex:** This complex of proteins binds to telomeres and protects them from degradation and inappropriate recombination. It also acts as a scaffold for the recruitment of telomerase and other factors involved in telomere maintenance.
3. **DNA Repair Pathways:** Telomeres are susceptible to DNA damage, which can lead to telomere shortening or dysfunction. DNA repair pathways, including non-homologous end joining (NHEJ) and homologous recombination (HR), can help repair telomere damage and maintain their integrity.
4. **Transcriptional Regulation:** The expression of telomere-associated genes, including telomerase, shelterin components, and DNA repair factors, is tightly regulated by transcription factors and signaling pathways. Factors like MYC, p53, and the Wnt pathway play roles in controlling telomere maintenance.
5. **Post-translational Modifications:** Proteins involved in telomere maintenance undergo various post-translational modifications, including phosphorylation, acetylation, and ubiquitination, which can influence their activity and localization.
In summary, positive regulation of telomere maintenance involves a multifaceted process that ensures the proper function of telomeres, enabling cells to divide and maintain genomic stability. Disruptions in this process can lead to premature aging, genomic instability, and increased cancer risk. Understanding the mechanisms underlying telomere maintenance is crucial for developing therapies for aging-related diseases and cancer.'
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Proteins (2)
| Protein | Definition | Taxonomy |
|---|---|---|
| Protection of telomeres protein 1 | A protection of telomeres protein 1 that is encoded in the genome of human. [PRO:CNx, Reactome:R-HSA-174890] | Homo sapiens (human) |
| NAD-dependent protein deacetylase sirtuin-6 | An NAD-dependent protein deacylase sirtuin-6 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8N6T7] | Homo sapiens (human) |
Compounds (10)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| niacinamide | nicotinamide : A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group. | pyridine alkaloid; pyridinecarboxamide; vitamin B3 | anti-inflammatory agent; antioxidant; cofactor; EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor; EC 3.5.1.98 (histone deacetylase) inhibitor; Escherichia coli metabolite; geroprotector; human urinary metabolite; metabolite; mouse metabolite; neuroprotective agent; Saccharomyces cerevisiae metabolite; Sir2 inhibitor |
| pyrazinamide | pyrazinecarboxamide : A monocarboxylic acid amide resulting from the formal condensation of the carboxy group of pyrazinoic acid (pyrazine-2-carboxylic acid) with ammonia. A prodrug for pyrazinoic acid, pyrazinecarboxamide is used as part of multidrug regimens for the treatment of tuberculosis. | monocarboxylic acid amide; N-acylammonia; pyrazines | antitubercular agent; prodrug |
| pyrazinoic acid | pyrazine-2-carboxylic acid : The parent compound of the class of pyrazinecarboxylic acids, that is pyrazine bearing a single carboxy substituent. The active metabolite of the antitubercular drug pyrazinamide. pyrazinoic acid: active metabolite of pyrazinamide; structure | pyrazinecarboxylic acid | antitubercular agent; drug metabolite |
| 1-(4-nitrophenyl)piperazine | 1-(4-nitrophenyl)piperazine: structure in first source | ||
| rubimaillin | rubimaillin : A benzochromene that is 2H-benzo[h]chromene which is substituted by two methyl groups at position 2, a methoxycarbonyl group at position 5, and a hydroxy group at position 6. Found in the Chinese medical plant Rubia cordifola, It has an anti-cancer effect by inhibition of TNF-alpha-induced NF-kappaB activation. It is also a dual inhibitor of acyl-CoA:cholesterol acyltransferase 1 and 2 (ACAT1 and ACAT2), but is more selective for the ACAT2 isozyme. rubimaillin: structure given in first source | benzochromene; methyl ester; phenols | acyl-CoA:cholesterol acyltransferase 2 inhibitor; anti-inflammatory agent; antineoplastic agent; apoptosis inducer; neuroprotective agent; NF-kappaB inhibitor; plant metabolite |
| 5-chloropyrazinamide | |||
| trichostatin a | trichostatin A: chelates zinc ion in the active site of histone deacetylases, resulting in preventing histone unpacking so DNA is less available for transcription; do not confuse with TRICHOSANTHIN which is a protein; found in STREPTOMYCES | antibiotic antifungal agent; hydroxamic acid; trichostatin | bacterial metabolite; EC 3.5.1.98 (histone deacetylase) inhibitor; geroprotector |
| (3R,5S)-fluvastatin | (3R,5S)-fluvastatin : A (6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoic acid diastereoisomer in which the stereocentres beta- and delta- to the carboxy group have R and S configuration, respectively. The drug fluvastatin is an equimolar mixture of this compound and its enantiomer. | (6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoic acid; statin (synthetic) | |
| braco-19 | BRACO-19: structure in first source | acridines; N-alkylpyrrolidine | |
| ly2784544 | pyridazines |