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nucleotide-excision repair, DNA gap filling
Definition
Target type: biologicalprocess
Repair of the gap in the DNA helix by DNA polymerase and DNA ligase after the portion of the strand containing the lesion has been removed by pyrimidine-dimer repair enzymes. [ISBN:0815316194]
Nucleotide-excision repair (NER) is a critical DNA repair pathway that removes damaged or modified nucleotides from the genome. It involves a series of steps:
1. **Damage Recognition:** Specialized proteins, including XPC-RAD23B and DDB2-DDB1, scan the DNA for bulky lesions, such as those caused by UV radiation or chemical mutagens. These proteins identify distortions in the DNA helix caused by the damage.
2. **Excision:** Once the damage is recognized, a multi-protein complex, including XPA and TFIIH, is recruited to the site. TFIIH possesses helicase activity, which unwinds the DNA around the damage, while XPA stabilizes the complex. Then, an endonuclease complex consisting of XPG and ERCC1-XPF makes two incisions on either side of the damage, excising a short oligonucleotide containing the damaged nucleotides.
3. **Gap Filling:** After the damaged segment is removed, the resulting gap is filled by DNA polymerase delta or epsilon, using the intact complementary strand as a template. This process involves the addition of new nucleotides that are complementary to the template strand, restoring the original DNA sequence.
4. **Ligation:** Finally, the newly synthesized DNA segment is joined to the surrounding DNA by DNA ligase, sealing the gap and restoring the integrity of the DNA molecule.
NER plays a crucial role in maintaining the stability of the genome, protecting against mutations, and preventing diseases such as cancer. The gap filling step is essential for restoring the correct nucleotide sequence and ensuring that the DNA is fully repaired.
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Proteins (3)
| Protein | Definition | Taxonomy |
|---|---|---|
| DNA polymerase kappa | A DNA polymerase kappa that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9UBT6] | Homo sapiens (human) |
| DNA polymerase delta catalytic subunit | A DNA polymerase delta catalytic subunit that is encoded in the genome of human. [PRO:DNx, UniProtKB:P28340] | Homo sapiens (human) |
| DNA polymerase beta | A DNA polymerase beta that is encoded in the genome of human. [PRO:CNA] | Homo sapiens (human) |
Compounds (31)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| digallic acid | digallic acid: structure given in first source | benzoate ester; gallate ester | |
| candesartan cilexetil | candesartan cilexetil: a prodrug which is metabolized to an active form candesartan to exert its biological effects | biphenyls | |
| foscarnet | Foscarnet: An antiviral agent used in the treatment of cytomegalovirus retinitis. Foscarnet also shows activity against human herpesviruses and HIV. phosphonoformic acid : Phosphoric acid in which one of the hydroxy groups is replaced by a carboxylic acid group. It is used as the trisodium salt as an antiviral agent in the treatment of cytomegalovirus retinitis (CMV retinitis, an inflamation of the retina that can lead to blindness) and as an alternative to ganciclovir for AIDS patients who require concurrent antiretroviral therapy but are unable to tolerate ganciclovir due to haematological toxicity. | carboxylic acid; one-carbon compound; phosphonic acids | antiviral drug; geroprotector; HIV-1 reverse transcriptase inhibitor; sodium-dependent Pi-transporter inhibitor |
| pamoic acid | pamoic acid: RN given refers to parent cpd; structure | dicarboxylic acid | |
| Dillapiole | 5-allyl 6,7-dimethoxy 1,3-benzodioxole: a plant based insecticide; structure in first source | benzodioxoles | metabolite |
| oleanolic acid | hydroxy monocarboxylic acid; pentacyclic triterpenoid | plant metabolite | |
| ochracin | ochracin: produced by Aspergillus alutaceus; structure in first source | isochromanes | |
| zidovudine | zidovudine : A pyrimidine 2',3'-dideoxyribonucleoside compound having a 3'-azido substituent and thymine as the nucleobase. Zidovudine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. | azide; pyrimidine 2',3'-dideoxyribonucleoside | antimetabolite; antiviral drug; HIV-1 reverse transcriptase inhibitor |
| ursolic acid | hydroxy monocarboxylic acid; pentacyclic triterpenoid | geroprotector; plant metabolite | |
| thymidine 5'-triphosphate | dTTP : A thymidine phosphate having a triphosphate group at the 5'-position. thymidine 5'-triphosphate: RN given refers to parent cpd | pyrimidine 2'-deoxyribonucleoside 5'-triphosphate; thymidine phosphate | Escherichia coli metabolite; mouse metabolite |
| betulinic acid | hydroxy monocarboxylic acid; pentacyclic triterpenoid | anti-HIV agent; anti-inflammatory agent; antimalarial; antineoplastic agent; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; plant metabolite | |
| calanolide a | (+)-calanolide A : An organic heterotetracyclic compound that is 11,12-dihydro-2H,6H,10H-dipyrano[2,3-f:2',3'-h]chromen-2-one substituted by a hydroxy group at position 12, methyl groups at positions 6, 6, 10 and 11 and a propyl group at position 4 (the 10R,11S,12S stereoisomer). Isolated from Calophyllum lanigerum var austrocoriaceum and Calophyllum brasiliense, it exhibits potent activity against HIV-1 reverse transcriptase. calanolide A: NSC 661122 and costatolide are isomers; a novel HIV-inhibitory class of coumarin derivatives from the tropical rainforest tree, Calophyllum lanigerum (Clusiaceae); structure in first source | cyclic ether; delta-lactone; organic heterotetracyclic compound; secondary alcohol | HIV-1 reverse transcriptase inhibitor; plant metabolite |
| 2',3'-dideoxythymidine triphosphate | ddTTP : A pyrimidine 2',3'-dideoxyribonucleoside 5'-triphosphate having thymine as the nucleobase. | pyrimidine 2',3'-dideoxyribonucleoside 5'-triphosphate; thymidine phosphate | |
| 2',3'-dideoxyadenosine triphosphate | purine deoxyribonucleoside triphosphate | ||
| zidovudine triphosphate | |||
| illimaquinone | illimaquinone: structure given in first source; isolated from the Red Sea sponge Smenospongia; inhibits the RNase H. activity of HIV-1 reverse transcriptase | monohydroxy-1,4-benzoquinones; prenylquinone | metabolite |
| sitosterol, (3beta)-isomer | sitosterol : A member of the class of phytosterols that is stigmast-5-ene substituted by a beta-hydroxy group at position 3. Sobatum: tradename; active fraction of Solanum trilobatum; reduces side-effects of radiation-induced toxicity | 3beta-hydroxy-Delta(5)-steroid; 3beta-sterol; C29-steroid; phytosterols; stigmastane sterol | anticholesteremic drug; antioxidant; mouse metabolite; plant metabolite; sterol methyltransferase inhibitor |
| TTP | pyrimidine ribonucleoside 5'-triphosphate | ||
| aphidicolin | aphidicolin : A tetracyclic diterpenoid that has an tetradecahydro-8,11a-methanocyclohepta[a]naphthalene skeleton with two hydroxymethyl substituents at positions 4 and 9, two methyl substituents at positions 4 and 11b and two hydroxy substituents at positions 3 and 9. An antibiotic with antiviral and antimitotical properties. Aphidicolin is a reversible inhibitor of eukaryotic nuclear DNA replication. Aphidicolin: An antiviral antibiotic produced by Cephalosporium aphidicola and other fungi. It inhibits the growth of eukaryotic cells and certain animal viruses by selectively inhibiting the cellular replication of DNA polymerase II or the viral-induced DNA polymerases. The drug may be useful for controlling excessive cell proliferation in patients with cancer, psoriasis or other dermatitis with little or no adverse effect upon non-multiplying cells. | tetracyclic diterpenoid | antimicrobial agent; antimitotic; antineoplastic agent; antiviral drug; apoptosis inducer; Aspergillus metabolite; DNA synthesis inhibitor; EC 2.7.7.7 (DNA-directed DNA polymerase) inhibitor; fungal metabolite |
| pnu183792 | PNU183792: structure in first source | ||
| stigmasterol | stigmasta-5,22-dien-3-ol: isolated from freeze-dried powder of Blackberries (Rubus ursinus L.) which showed an activity on inhibition of chemocarcinogen stigmasterol : A 3beta-sterol that consists of 3beta-hydroxystigmastane having double bonds at the 5,6- and 22,23-positions. | 3beta-hydroxy-Delta(5)-steroid; 3beta-sterol; phytosterols; stigmastane sterol | plant metabolite |
| pecilocin | pecilocin: fungicidal antibiotic produced by Paecilomyces varioti Bainier var. antibioticus; structure | N-acylpyrrolidine | |
| lyoniside | daucosterol : A steroid saponin that is sitosterol attached to a beta-D-glucopyranosyl residue at position 3 via a glycosidic linkage. It has bee isolated from Panax japonicus var. major and Breynia fruticosa. | beta-D-glucoside; monosaccharide derivative; steroid saponin | plant metabolite |
| manoalide | manoalide : A sesterterpenoid isolated from the marine sponge Luffariella variabilis and which has been shown to exhibit inhibitory activity towards phospholipase A2. manoalide: phospholipase A2 inhibitor; sesterterpene from marine sponge L. variabilis; structure given in first source | butenolide; lactol; sesterterpenoid | EC 3.1.1.4 (phospholipase A2) inhibitor; EC 5.99.1.2 (DNA topoisomerase) inhibitor; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; metabolite |
| corosolic acid | triterpenoid | metabolite | |
| 3-o-methylfunicone | 3-O-methylfunicone: derived from Penicillium pinophilum; structure in first source | ||
| edgeworin | edgeworin: from Dirca occidentalis Gray; structure given in first source | ||
| sch 725680 | Sch 725680: an aazaphilone from Aspergillus sp.; structure in first source | ||
| raltegravir | 1,2,4-oxadiazole; dicarboxylic acid amide; hydroxypyrimidine; monofluorobenzenes; pyrimidone; secondary carboxamide | antiviral drug; HIV-1 integrase inhibitor | |
| GS-443902 | GS-441524 triphosphate: intracellular active metabolite of remdesivir GS-443902 : An organic triphosphate that is GS-441524 in which the 5'-hydroxy group has been replaced by a triphosphate group. It is the active metabolite of remdesivir. | aromatic amine; C-nucleoside; nitrile; organic triphosphate; pyrrolotriazine | anticoronaviral agent; antiviral drug; drug metabolite |
| pinophilin b | pinophilin B: from cultures of a fungus (Penicillium pinophilum Hedgcok) derived from a seaweed; structure in first source |