Page last updated: 2024-10-24

negative regulation of telomere capping

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of telomere capping. [GO_REF:0000058, GOC:BHF, GOC:BHF_telomere, GOC:nc, GOC:TermGenie, PMID:23959892]

Negative regulation of telomere capping is a complex process that involves a delicate balance of enzymatic activities and protein interactions to ensure the proper maintenance of telomeres, the protective caps at the ends of chromosomes. Telomeres are composed of repetitive DNA sequences and associated proteins that prevent chromosome ends from being recognized as DNA breaks, which can lead to DNA degradation, chromosome fusion, and genomic instability.

The process of negative regulation of telomere capping involves the downregulation or inhibition of factors that promote telomere capping. This can occur through various mechanisms:

1. **Inhibition of telomerase activity:** Telomerase is a specialized enzyme responsible for adding repetitive DNA sequences to the ends of chromosomes, thereby lengthening telomeres. Negative regulation of telomere capping can involve inhibiting telomerase activity through various mechanisms, such as:
* **Regulation of telomerase expression:** Transcriptional or translational repression of telomerase genes can reduce telomerase levels.
* **Inhibition of telomerase catalytic activity:** Specific inhibitors can bind to the active site of telomerase, preventing its enzymatic activity.
* **Disruption of telomerase recruitment to telomeres:** Factors that interfere with the localization of telomerase to telomeres can prevent telomere extension.

2. **Promotion of telomere degradation:** Negative regulation of telomere capping can also involve promoting telomere degradation by:
* **Activation of nucleases:** Specific nucleases, such as exonucleases, can degrade telomeric DNA sequences, shortening telomeres.
* **Induction of DNA damage:** Exposure to certain environmental stressors or cellular insults can induce DNA damage at telomeres, leading to their degradation.

3. **Disruption of telomere-binding proteins:** Telomeres are bound by a complex network of proteins that contribute to their structure and function. Negative regulation of telomere capping can involve:
* **Dissociation of protective proteins:** Factors that promote the dissociation of telomere-binding proteins can leave telomeres vulnerable to degradation or inappropriate processing.
* **Recruitment of repair proteins:** The disruption of telomere-binding proteins can trigger the recruitment of DNA repair proteins, which may not be suitable for telomere maintenance and can lead to inappropriate processing or shortening of telomeres.

4. **Altered chromatin structure:** The chromatin structure at telomeres is crucial for their proper function. Negative regulation of telomere capping can involve:
* **Chromatin remodeling:** Changes in the chromatin structure at telomeres, such as increased compaction or altered histone modifications, can affect telomere accessibility and function.
* **Transcriptional silencing:** The altered chromatin structure can also lead to transcriptional silencing of telomere-associated genes, contributing to negative regulation of telomere capping.

The negative regulation of telomere capping is a crucial process that contributes to maintaining the integrity of the genome. It plays a role in various cellular processes, including cell proliferation, senescence, and apoptosis. Dysregulation of telomere capping can lead to genomic instability and various diseases, including cancer. Therefore, understanding the intricate mechanisms of negative regulation of telomere capping is essential for unraveling the complexities of cellular aging and disease pathogenesis.'
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Proteins (1)

ProteinDefinitionTaxonomy
Serine-protein kinase ATMA serine-protein kinase ATM that is encoded in the genome of human. [PRO:CNA]Homo sapiens (human)

Compounds (20)

CompoundDefinitionClassesRoles
pd 173074aromatic amine;
biaryl;
dimethoxybenzene;
pyridopyrimidine;
tertiary amino compound;
ureas
antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
fibroblast growth factor receptor antagonist
caffeinepurine alkaloid;
trimethylxanthine
adenosine A2A receptor antagonist;
adenosine receptor antagonist;
adjuvant;
central nervous system stimulant;
diuretic;
EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor;
EC 3.1.4.* (phosphoric diester hydrolase) inhibitor;
environmental contaminant;
food additive;
fungal metabolite;
geroprotector;
human blood serum metabolite;
mouse metabolite;
mutagen;
plant metabolite;
psychotropic drug;
ryanodine receptor agonist;
xenobiotic
2-(4-morpholinyl)-8-phenyl-4h-1-benzopyran-4-one2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one: specific inhibitor of phosphatidylinositol 3-kinase; structure in first sourcechromones;
morpholines;
organochlorine compound
autophagy inhibitor;
EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor;
geroprotector
schizandrin bschizandrin B: a phytogenic antineoplastic agent with anti-inflammatory activity; isolated from Schisandra plant
thioureathiourea : The simplest member of the thiourea class, consisting of urea with the oxygen atom substituted by sulfur.

Thiourea: A photographic fixative used also in the manufacture of resins. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance may reasonably be anticipated to be a carcinogen (Merck Index, 9th ed). Many of its derivatives are ANTITHYROID AGENTS and/or FREE RADICAL SCAVENGERS.
one-carbon compound;
thioureas;
ureas
antioxidant;
chromophore
ku 559332-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one: specific inhibitor of the ataxia-telangiectasia mutated kinase ATM; structure in first source
cgk 733diarylmethane
nu 70262-(morpholin-4-yl)benzo(h)chromen-4-one: a radiosensitizing agent that inhibits DNA-dependent protein kinase; structure in first sourceorganic heterotricyclic compound;
organooxygen compound
nu 74418-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one: structure in first sourcedibenzothiophenes
ku-0060648dibenzothiophenes
dactolisibdactolisib : An imidazoquinoline that is 3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinoline substituted at position 1 by a 4-(1-cyanoisopropyl)phenyl group and at position 8 by a quinolin-3-yl group. A dual PI3K/mTOR inhibitor used in cancer treatment.

dactolisib: antineoplastic agent that inhibits both phosphatidylinositol 3-kinase and mTOR
imidazoquinoline;
nitrile;
quinolines;
ring assembly;
ureas
antineoplastic agent;
EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor;
mTOR inhibitor
ku 60019
cp 466722quinazolines
(3R)-4-[2-(1H-indol-4-yl)-6-(1-methylsulfonylcyclopropyl)-4-pyrimidinyl]-3-methylmorpholineindoles
ve 8213-amino-6-(4-(methylsulfonyl)phenyl)-N-phenylpyrazine-2-carboxamide: an antineoplastic agent; structure in first sourcearomatic amide
torin 2torin 2 : A member of the class of pyridoquinolines that is benzo[h][1,6]naphthyridin-2-one carrying additional 3-(trifluoromethyl)phenyl and 6-aminopyridin-3-yl substituents at positions 1 and 9 respectively. It is a potent inhibitor of mTOR and exhibits anti-cancer properties.aminopyridine;
organofluorine compound;
primary amino compound;
pyridoquinoline
antineoplastic agent;
mTOR inhibitor
byl719proline derivative
cc-1151-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino(2,3-b)pyrazin-2(1H)-one: an mTOR kinase inhibitor; structure in first source
vx-970berzosertib: an ATR kinase inhibitorsulfonamide
etp-46464ETP-46464: inhibits ATM and Rad3-related kinase; structure in first source