Page last updated: 2024-10-24

pyrimidine dimer repair

Definition

Target type: biologicalprocess

The repair of UV-induced T-T, C-T and C-C dimers. [ISBN:0815316194]

Pyrimidine dimers are a type of DNA damage caused by ultraviolet (UV) radiation. They are formed when two adjacent pyrimidine bases, typically thymine, in the same DNA strand become covalently linked. This damage can disrupt DNA replication and transcription, leading to cell death or mutations. The repair of pyrimidine dimers is crucial for maintaining genome integrity and preventing disease. This process, called nucleotide excision repair (NER), is a complex multi-step pathway that involves the following steps:

1. Recognition and Verification: The damage is first recognized by specific proteins called damage recognition factors. In eukaryotes, these include XPC-RAD23B and DDB1-DDB2. The XPC-RAD23B complex binds to the distorted DNA structure caused by the dimer. DDB1-DDB2 binds to damaged DNA in a UV-dependent manner, and it is particularly efficient at removing cyclobutane pyrimidine dimers (CPDs). These complexes recruit other repair proteins to the site of damage.
2. Incision: Once the damage is recognized, two incisions are made in the DNA strand, one on each side of the dimer. The incisions are made by specialized nucleases, in humans these are known as ERCC1-XPF and XPG. They create a small single-stranded gap containing the damaged DNA.
3. Excision: The damaged DNA segment, including the pyrimidine dimer, is excised from the DNA strand by a helicase, known as DNA2 in humans.
4. Resynthesis: The gap created by excision is filled in by DNA polymerase using the undamaged complementary strand as a template.
5. Ligation: The newly synthesized DNA segment is joined to the original DNA strand by DNA ligase, sealing the gap and restoring the integrity of the DNA molecule.

The NER pathway is highly conserved across species, suggesting its essential role in protecting life from the damaging effects of UV radiation. Mutations in NER genes can lead to genetic disorders, including xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD). These disorders are characterized by increased sensitivity to UV radiation, a predisposition to skin cancer, and other developmental abnormalities.'
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Proteins (2)

ProteinDefinitionTaxonomy
DNA polymerase etaA DNA polymerase eta that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y253]Homo sapiens (human)
DNA polymerase betaA DNA polymerase beta that is encoded in the genome of human. [PRO:CNA]Homo sapiens (human)

Compounds (27)

CompoundDefinitionClassesRoles
digallic aciddigallic acid: structure given in first sourcebenzoate ester;
gallate ester
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
candesartan cilexetilcandesartan cilexetil: a prodrug which is metabolized to an active form candesartan to exert its biological effectsbiphenyls
pamoic acidpamoic acid: RN given refers to parent cpd; structuredicarboxylic acid
Dillapiole5-allyl 6,7-dimethoxy 1,3-benzodioxole: a plant based insecticide; structure in first sourcebenzodioxolesmetabolite
oleanolic acidhydroxy monocarboxylic acid;
pentacyclic triterpenoid
plant metabolite
zidovudinezidovudine : 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 acidhydroxy monocarboxylic acid;
pentacyclic triterpenoid
geroprotector;
plant metabolite
thymidine 5'-triphosphatedTTP : 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 acidhydroxy 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 triphosphateddTTP : A pyrimidine 2',3'-dideoxyribonucleoside 5'-triphosphate having thymine as the nucleobase.pyrimidine 2',3'-dideoxyribonucleoside 5'-triphosphate;
thymidine phosphate
2',3'-dideoxyadenosine triphosphatepurine deoxyribonucleoside triphosphate
zidovudine triphosphate
illimaquinoneillimaquinone: structure given in first source; isolated from the Red Sea sponge Smenospongia; inhibits the RNase H. activity of HIV-1 reverse transcriptasemonohydroxy-1,4-benzoquinones;
prenylquinone
metabolite
sitosterol, (3beta)-isomersitosterol : 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
TTPpyrimidine ribonucleoside 5'-triphosphate
aphidicolinaphidicolin : 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 diterpenoidantimicrobial 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
stigmasterolstigmasta-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
ellagic acidcatechols;
cyclic ketone;
lactone;
organic heterotetracyclic compound;
polyphenol
antioxidant;
EC 1.14.18.1 (tyrosinase) inhibitor;
EC 2.3.1.5 (arylamine N-acetyltransferase) inhibitor;
EC 2.4.1.1 (glycogen phosphorylase) inhibitor;
EC 2.5.1.18 (glutathione transferase) inhibitor;
EC 2.7.1.127 (inositol-trisphosphate 3-kinase) inhibitor;
EC 2.7.1.151 (inositol-polyphosphate multikinase) inhibitor;
EC 2.7.4.6 (nucleoside-diphosphate kinase) inhibitor;
EC 2.7.7.7 (DNA-directed DNA polymerase) inhibitor;
EC 5.99.1.2 (DNA topoisomerase) inhibitor;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
food additive;
fungal metabolite;
geroprotector;
plant metabolite;
skin lightening agent
pecilocinpecilocin: fungicidal antibiotic produced by Paecilomyces varioti Bainier var. antibioticus; structureN-acylpyrrolidine
lyonisidedaucosterol : 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
corosolic acidtriterpenoidmetabolite
3-o-methylfunicone3-O-methylfunicone: derived from Penicillium pinophilum; structure in first source
edgeworinedgeworin: from Dirca occidentalis Gray; structure given in first source
raltegravir1,2,4-oxadiazole;
dicarboxylic acid amide;
hydroxypyrimidine;
monofluorobenzenes;
pyrimidone;
secondary carboxamide
antiviral drug;
HIV-1 integrase inhibitor
GS-443902GS-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