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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Protein | Definition | Taxonomy |
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DNA-(apurinic or apyrimidinic site) endonuclease | A DNA-(apurinic or apyrimidinic site) endonuclease that is encoded in the genome of human. [PRO:DNx, UniProtKB:P27695] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
aurintricarboxylic acid | aurintricarboxylic 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 |
hycanthone | hycanthone : 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. | thioxanthenes | mutagen; schistosomicide drug |
lucanthone | lucanthone : 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) | thioxanthenes | adjuvant; 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 hydrochloride | hydrochloride | antineoplastic agent | |
7-nitro-1h-indole-2-carboxylic acid | 7-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-hydroxydopa | 6-hydroxydopa: RN given refers to cpd without isomeric designation | non-proteinogenic alpha-amino acid | |
tanshinone ii a | tashinone IIA: a cardiovascular agent with antineoplastic activity; isolated from Salvia miltiorrhiza; structure in first source | abietane diterpenoid | |
1,3,6-trimethylpyrimido[5,4-e][1,2,4]triazine-5,7-dione | pyrimidotriazine | ||
2-[[5-(dimethylsulfamoyl)-1H-indol-3-yl]methylidene]propanedioic acid diethyl ester | indoles | ||
1,6-dimethyl-3-propylpyrimido[5,4-e][1,2,4]triazine-5,7-dione | pyrimidotriazine | ||
myricetin | 7-hydroxyflavonol; hexahydroxyflavone | antineoplastic agent; antioxidant; cyclooxygenase 1 inhibitor; food component; geroprotector; hypoglycemic agent; plant metabolite | |
ag 538 | AG 538: an IGF-1 receptor kinase inhibitor; structure in first source | ||
e 3330 | E 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]acetamide | benzothiazoles | ||
thiolactomycin | thiolactomycin: from actinomycetes; structure given in first source | ||
galloflavin | galloflavin: structure in first source |