Page last updated: 2024-10-24

telomere maintenance via base-excision repair

Definition

Target type: biologicalprocess

A telomere maintenance process that occurs by base-excision repair of telomeric DNA in response to DNA damage. Telomeric sequences are particularly susceptible to oxidative DNA damage, due to their G-rich nature. [GOC:BHF, GOC:BHF_telomere, GOC:jbu, PMID:24703901]

Telomere maintenance via base-excision repair (BER) is a specialized pathway that counteracts the gradual shortening of telomeres that occurs with each cell division. Unlike the classic BER pathway, which primarily removes damaged bases from the genome, telomeric BER focuses on maintaining the integrity of the G-rich telomere overhang. Here's how it works:

1. **Recognition of Damage:** Telomeres are particularly susceptible to oxidative stress, which can lead to the formation of abasic sites (missing bases) within the G-rich overhang. These sites are recognized by specific DNA glycosylases, such as NEIL1 and OGG1, which remove the damaged base, leaving an abasic site.

2. **AP Endonuclease Activity:** The abasic site is then processed by an AP endonuclease, which cleaves the DNA backbone 5' to the abasic site. This creates a single-strand break with a 5' deoxyribose phosphate (dRP) group.

3. **dRP Removal and Gap Filling:** The dRP group is then removed by a specialized enzyme called dRP lyase, which is often part of the same protein as the AP endonuclease. This leaves a 3' hydroxyl group at the break site. The resulting gap is then filled in by DNA polymerase, using the complementary strand as a template.

4. **Ligase Action:** Finally, the nick is sealed by DNA ligase, restoring the integrity of the telomere.

This BER-mediated telomere maintenance pathway helps to preserve telomere length by efficiently repairing oxidative damage and preventing the accumulation of detrimental lesions. This mechanism is essential for maintaining genomic stability and cellular function.
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Proteins (1)

ProteinDefinitionTaxonomy
DNA-(apurinic or apyrimidinic site) endonucleaseA DNA-(apurinic or apyrimidinic site) endonuclease that is encoded in the genome of human. [PRO:DNx, UniProtKB:P27695]Homo sapiens (human)

Compounds (17)

CompoundDefinitionClassesRoles
aurintricarboxylic acidaurintricarboxylic acid : A member of the class of quinomethanes that is 3-methylidene-6-oxocyclohexa-1,4-diene-1-carboxylic acid in which the methylidene hydrogens are replaced by 4-carboxy-3-hydroxyphenyl groups. The trisodium salt is the biological stain 'chrome violet CG' while the triammonium salt is 'aluminon'.

Aurintricarboxylic Acid: A dye which inhibits protein biosynthesis at the initial stages. The ammonium salt (aluminon) is a reagent for the colorimetric estimation of aluminum in water, foods, and tissues.
monohydroxybenzoic acid;
quinomethanes;
tricarboxylic acid
fluorochrome;
histological dye;
insulin-like growth factor receptor 1 antagonist
hycanthonehycanthone : A thioxanthen-9-one compound having a hydroxymethyl substituent at the 1-position and a 2-[(diethylamino)ethyl]amino substituent at the 4-position. It was formerly used (particularly as the monomethanesulfonic acid salt) as a schistosomicide for individual or mass treatement of infection with Schistosoma haematobium and S. mansoni, but due to its toxicity and concern about possible carcinogenicity, it has been replaced by other drugs such as praziquantel.

Hycanthone: Potentially toxic, but effective antischistosomal agent, it is a metabolite of LUCANTHONE.
thioxanthenesmutagen;
schistosomicide drug
lucanthonelucanthone : A thioxanthen-9-one compound having a methyl substituent at the 1-position and a 2-[(diethylamino)ethyl]amino substituent at the 4-position. Formerly used for the treatment of schistosomiasis. It is a prodrug, being metabolised to hycanthone.

Lucanthone: One of the SCHISTOSOMICIDES, it has been replaced largely by HYCANTHONE and more recently PRAZIQUANTEL. (From Martindale The Extrapharmacopoeia, 30th ed., p46)
thioxanthenesadjuvant;
antineoplastic agent;
EC 5.99.1.2 (DNA topoisomerase) inhibitor;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
mutagen;
photosensitizing agent;
prodrug;
schistosomicide drug
mitoxantrone hydrochloridehydrochlorideantineoplastic agent
7-nitro-1h-indole-2-carboxylic acid7-nitro-1H-indole-2-carboxylic acid: acts on AP endonuclease, 3'-phosphodiesterase, and 3'-phosphatase activities of APE1; structure in first source
3,3',4,4',5,5'-hexabromobiphenyl
6-hydroxydopa6-hydroxydopa: RN given refers to cpd without isomeric designationnon-proteinogenic alpha-amino acid
tanshinone ii atashinone IIA: a cardiovascular agent with antineoplastic activity; isolated from Salvia miltiorrhiza; structure in first sourceabietane diterpenoid
1,3,6-trimethylpyrimido[5,4-e][1,2,4]triazine-5,7-dionepyrimidotriazine
2-[[5-(dimethylsulfamoyl)-1H-indol-3-yl]methylidene]propanedioic acid diethyl esterindoles
1,6-dimethyl-3-propylpyrimido[5,4-e][1,2,4]triazine-5,7-dionepyrimidotriazine
myricetin7-hydroxyflavonol;
hexahydroxyflavone
antineoplastic agent;
antioxidant;
cyclooxygenase 1 inhibitor;
food component;
geroprotector;
hypoglycemic agent;
plant metabolite
ag 538AG 538: an IGF-1 receptor kinase inhibitor; structure in first source
e 3330E 3330: structure given in first source; MW 378.47
N-[3-(1,3-benzothiazol-2-yl)-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl]acetamidebenzothiazoles
thiolactomycinthiolactomycin: from actinomycetes; structure given in first source
galloflavingalloflavin: structure in first source