positive regulation of telomere maintenance in response to DNA damage
Definition
Target type: biologicalprocess
Any process that activates or increases the frequency, rate or extent of telomere maintenance in response to DNA damage. [GO_REF:0000058, GOC:BHF, GOC:BHF_telomere, GOC:nc, GOC:TermGenie, PMID:22579284]
Positive regulation of telomere maintenance in response to DNA damage is a complex biological process that involves a coordinated effort of multiple cellular pathways to ensure the stability and integrity of telomeres, the protective caps at the ends of chromosomes, following DNA damage.
DNA damage, a ubiquitous threat to genome integrity, can trigger telomere dysfunction, leading to chromosome instability and cell senescence. To counteract this, cells have evolved sophisticated mechanisms to safeguard telomeres from damage and to promote their repair and maintenance.
The process begins with the detection of DNA damage at telomeres. Specialized proteins, including DNA damage sensors and checkpoint kinases, recognize the damage and initiate a signaling cascade that triggers cell cycle arrest, allowing time for repair. This arrest is crucial to prevent the propagation of damaged DNA to daughter cells during replication.
The repair process involves a variety of DNA repair pathways, including homologous recombination (HR) and non-homologous end joining (NHEJ). HR is a high-fidelity mechanism that uses the undamaged sister chromatid as a template for repair, while NHEJ, although less precise, can join broken ends together.
In addition to DNA repair, the response to DNA damage also involves telomere lengthening through the activation of telomerase, an enzyme responsible for adding repetitive DNA sequences to the ends of chromosomes. Telomerase activity is tightly regulated, and its activation in response to DNA damage ensures that telomeres remain sufficiently long to protect chromosomes from degradation.
Furthermore, the response to DNA damage at telomeres involves the recruitment of specific factors that contribute to telomere maintenance. These factors include shelterin proteins, which protect telomeres from degradation and inappropriate recombination, and factors involved in telomere capping, which prevents the ends of chromosomes from being recognized as broken DNA.
The intricate interplay of these various pathways, involving DNA damage sensing, cell cycle arrest, DNA repair, telomere lengthening, and telomere protection, ensures that telomeres are effectively maintained and stabilized in the face of DNA damage, preventing genomic instability and promoting cellular survival.'
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Proteins (3)
| Protein | Definition | Taxonomy |
|---|---|---|
| Ubiquitin carboxyl-terminal hydrolase isozyme L5 | A ubiquitin carboxyl-terminal hydrolase isozyme L5 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y5K5] | Homo sapiens (human) |
| RuvB-like 1 | A RuvB-like 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y265] | Homo sapiens (human) |
| RuvB-like 2 | A RuvB-like 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y230] | Homo sapiens (human) |
Compounds (6)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| tiaprofenic acid | tiaprofenic acid : An aromatic ketone that is thiophene substituted at C-2 by benzoyl and at C-4 by a 1-carboxyethyl group. tiaprofenic acid: RN given refers to parent cpd; structure | aromatic ketone; monocarboxylic acid; thiophenes | drug allergen; non-steroidal anti-inflammatory drug |
| celastrol | monocarboxylic acid; pentacyclic triterpenoid | anti-inflammatory drug; antineoplastic agent; antioxidant; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; Hsp90 inhibitor; metabolite | |
| sorafenib | (trifluoromethyl)benzenes; aromatic ether; monochlorobenzenes; phenylureas; pyridinecarboxamide | angiogenesis inhibitor; anticoronaviral agent; antineoplastic agent; EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor; ferroptosis inducer; tyrosine kinase inhibitor | |
| rottlerin | rottlerin : A chromenol that is 2,2-dimethyl-2H-chromene substituted by hydroxy groups at positions 5 and 7, a 3-acetyl-2,4,6-trihydroxy-5-methylbenzyl group at position 6 and a (1E)-3-oxo-1-phenylprop-1-en-3-yl group at position 8. A potassium channel opener, it is isolated from Mallotus philippensis. rottlerin: an angiogenesis inhibitor; an inhibitor of protein kinase Cdelta (PKCdelta) and calmodulin kinase III; RN refers to (E)-isomer; do not confuse this chalcone with an anthraquinone that is also called rottlerin (RN 481-72-1); | aromatic ketone; benzenetriol; chromenol; enone; methyl ketone | anti-allergic agent; antihypertensive agent; antineoplastic agent; apoptosis inducer; K-ATP channel agonist; metabolite |
| acetyl isogambogic acid | acetyl isogambogic acid: structure in first source | ||
| akt-i-1,2 compound | Akt-I-1,2 compound: an aminopeptidase P inhibitor; structure in first source |