Page last updated: 2024-10-24

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)

ProteinDefinitionTaxonomy
Ubiquitin carboxyl-terminal hydrolase isozyme L5A ubiquitin carboxyl-terminal hydrolase isozyme L5 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y5K5]Homo sapiens (human)
RuvB-like 1A RuvB-like 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y265]Homo sapiens (human)
RuvB-like 2A RuvB-like 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y230]Homo sapiens (human)

Compounds (6)

CompoundDefinitionClassesRoles
tiaprofenic acidtiaprofenic 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
celastrolmonocarboxylic 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
rottlerinrottlerin : 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 acidacetyl isogambogic acid: structure in first source
akt-i-1,2 compoundAkt-I-1,2 compound: an aminopeptidase P inhibitor; structure in first source