Page last updated: 2024-10-24

DNA synthesis involved in DNA repair

Definition

Target type: biologicalprocess

Synthesis of DNA that proceeds from the broken 3' single-strand DNA end and uses the homologous intact duplex as the template. [PMID:10357855]

DNA repair is a fundamental cellular process that maintains the integrity of the genome by correcting errors or damage that occur in DNA molecules. DNA synthesis plays a crucial role in this repair process, ensuring the accurate replication of the damaged or missing sequences.

Here is a detailed description of the biological process of DNA synthesis involved in DNA repair:

1. **Damage Recognition:** Specialized proteins, known as DNA repair enzymes, scan the genome for any abnormalities, such as double-strand breaks, single-strand breaks, base modifications, or cross-links. These proteins identify the damaged region and recruit other repair machinery.

2. **Excision Repair:** In many repair pathways, the damaged section of DNA is excised by specialized nucleases. For instance, in base excision repair (BER), a damaged base is removed by DNA glycosylase enzymes, creating an apurinic/apyrimidinic (AP) site. In nucleotide excision repair (NER), a larger segment of DNA containing the damage is removed by a complex of proteins.

3. **Gap Filling:** Once the damaged DNA is removed, the gap created needs to be filled with new, correct DNA sequences. This is where DNA synthesis comes in.

4. **DNA Polymerase Activity:** DNA polymerases, specialized enzymes, are responsible for synthesizing new DNA strands. They use the intact complementary strand as a template to create a new strand that is identical to the original. DNA polymerases add nucleotides to the 3' end of a growing DNA strand, using the base pairing rules (A with T and C with G).

5. **Primer Requirement:** DNA polymerases can only extend existing DNA strands, they cannot initiate synthesis de novo. Therefore, a short RNA primer (a short sequence of nucleotides) is synthesized by an enzyme called primase, which provides a 3' end for DNA polymerase to start adding nucleotides.

6. **Ligase Action:** Once the gap is filled, the newly synthesized DNA strand is joined to the existing DNA strand by DNA ligase. This enzyme seals the remaining nick in the DNA backbone, restoring the integrity of the DNA molecule.

7. **Repair Pathway Specificity:** Different DNA repair pathways utilize specific DNA polymerases with different properties. For example, in BER, DNA polymerase β is involved in filling small gaps, while in NER, DNA polymerase δ or ε are involved in filling larger gaps.

8. **Error Prone Polymerases:** Some DNA polymerases, known as "error-prone polymerases," are utilized in situations where DNA damage is extensive or when accurate replication is not possible due to cellular stress. These polymerases can tolerate more mismatches and can even synthesize DNA across damaged regions, although with a higher error rate.

In conclusion, DNA synthesis plays a critical role in DNA repair by precisely filling gaps created by the removal of damaged DNA sequences. This process ensures the integrity of the genome, preventing mutations, and maintaining cellular function and survival.'
"

Proteins (7)

ProteinDefinitionTaxonomy
DNA polymerase etaA DNA polymerase eta that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y253]Homo sapiens (human)
NAD-dependent protein deacetylase sirtuin-1An NAD-dependent protein deacetylase sirtuin-1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q96EB6]Homo sapiens (human)
Ribonucleoside-diphosphate reductase subunit M2 BA ribonucleoside-diphosphate reductase subunit M2 B that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q7LG56]Homo sapiens (human)
Werner syndrome ATP-dependent helicaseA bifunctional 3-5 exonuclease/ATP-dependent helicase WRN that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q14191]Homo sapiens (human)
DNA polymerase delta catalytic subunitA DNA polymerase delta catalytic subunit that is encoded in the genome of human. [PRO:DNx, UniProtKB:P28340]Homo sapiens (human)
Ribonucleoside-diphosphate reductase large subunitA ribonucleoside-diphosphate reductase large subunit that is encoded in the genome of human. [PRO:DNx, UniProtKB:P23921]Homo sapiens (human)
DNA polymerase alpha catalytic subunitA DNA polymerase alpha catalytic subunit that is encoded in the genome of human. [PRO:DNx]Homo sapiens (human)

Compounds (55)

CompoundDefinitionClassesRoles
digallic aciddigallic acid: structure given in first sourcebenzoate ester;
gallate ester
niacinamidenicotinamide : A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group.pyridine alkaloid;
pyridinecarboxamide;
vitamin B3
anti-inflammatory agent;
antioxidant;
cofactor;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
EC 3.5.1.98 (histone deacetylase) inhibitor;
Escherichia coli metabolite;
geroprotector;
human urinary metabolite;
metabolite;
mouse metabolite;
neuroprotective agent;
Saccharomyces cerevisiae metabolite;
Sir2 inhibitor
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
bisindolylmaleimide ibisindolylmaleimide I: a bis(indolyl)maleimide
bisindolylmaleimide vbisindolylmaleimide V: used as a negative control compound for protein kinase C inhibition; structure in first source;indoles
candesartan cilexetilcandesartan cilexetil: a prodrug which is metabolized to an active form candesartan to exert its biological effectsbiphenyls
foscarnetFoscarnet: 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
hydroxyureaone-carbon compound;
ureas
antimetabolite;
antimitotic;
antineoplastic agent;
DNA synthesis inhibitor;
EC 1.17.4.1 (ribonucleoside-diphosphate reductase) inhibitor;
genotoxin;
immunomodulator;
radical scavenger;
teratogenic agent
entinostatbenzamides;
carbamate ester;
primary amino compound;
pyridines;
substituted aniline
antineoplastic agent;
apoptosis inducer;
EC 3.5.1.98 (histone deacetylase) inhibitor
fenamic acidfenamic acid : An aminobenzoic acid that is the N-phenyl derivative of anthranilic acid. It acts as a parent skeleton for the synthesis of several non-steroidal anti-inflammatory drugs.

fenamic acid: has chloride and potassium channel-blocking activity; RN given refers to parent cpd
aminobenzoic acid;
secondary amino compound
membrane transport modulator
ro 31-8220Ro 31-8220: a protein kinase C inhibitorimidothiocarbamic ester;
indoles;
maleimides
EC 2.7.11.13 (protein kinase C) inhibitor
fenofibratebenzochromenone;
delta-lactone;
naphtho-alpha-pyrone
platelet aggregation inhibitor;
Sir2 inhibitor
suraminsuramin : A member of the class of phenylureas that is urea in which each of the amino groups has been substituted by a 3-({2-methyl-5-[(4,6,8-trisulfo-1-naphthyl)carbamoyl]phenyl}carbamoyl)phenyl group. An activator of both the rabbit skeletal muscle RyR1 and sheep cardiac RyR2 isoform ryanodine receptor channels, it has been used for the treatment of human African trypanosomiasis for over 100 years.

Suramin: A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties.
naphthalenesulfonic acid;
phenylureas;
secondary carboxamide
angiogenesis inhibitor;
antinematodal drug;
antineoplastic agent;
apoptosis inhibitor;
EC 2.7.11.13 (protein kinase C) inhibitor;
GABA antagonist;
GABA-gated chloride channel antagonist;
purinergic receptor P2 antagonist;
ryanodine receptor agonist;
trypanocidal drug
nadNADgeroprotector
uridine diphosphateUridine Diphosphate: A uracil nucleotide containing a pyrophosphate group esterified to C5 of the sugar moiety.pyrimidine ribonucleoside 5'-diphosphate;
uridine 5'-phosphate
Escherichia coli metabolite;
mouse metabolite
cytidine diphosphateCytidine Diphosphate: Cytidine 5'-(trihydrogen diphosphate). A cytosine nucleotide containing two phosphate groups esterified to the sugar moiety. Synonyms: CRPP; cytidine pyrophosphate.cytidine 5'-phosphate;
pyrimidine ribonucleoside 5'-diphosphate
Escherichia coli metabolite;
mouse metabolite
4-tert-butylbenzoic acid4-tert-butylbenzoic acid: RN given refers to parent cpdalkylbenzene
suramin sodiumsuramin sodium : An organic sodium salt that is the hexasodium salt of suramin. It is an FDA approved drug for African sleeping sickness and river blindness.organic sodium saltangiogenesis inhibitor;
antinematodal drug;
antineoplastic agent;
apoptosis inhibitor;
EC 2.7.11.13 (protein kinase C) inhibitor;
GABA antagonist;
GABA-gated chloride channel antagonist;
purinergic receptor P2 antagonist;
ryanodine receptor agonist;
trypanocidal drug
ochracinochracin: produced by Aspergillus alutaceus; structure in first sourceisochromanes
toxoflavintoxoflavin : A pyrimidotriazine that is 1,6-dimethyl-1,5,6,7-tetrahydropyrimido[5,4-e][1,2,4]triazine with oxo groups at positions 5 and 7.

toxoflavin: azapteridine antibiotic; structure
carbonyl compound;
pyrimidotriazine
antibacterial agent;
antineoplastic agent;
apoptosis inducer;
bacterial metabolite;
toxin;
virulence factor;
Wnt signalling inhibitor
zidovudine triphosphate
paullonepaullone : An indolobenzazepine that is 5,6,7,12-tetrahydroindolo[3,2-d][1]benzazepine carrying an oxo substituent at position 6.

paullone: structure in first source
indolobenzazepine;
lactam
EC 2.7.11.22 (cyclin-dependent kinase) inhibitor;
EC 2.7.11.26 (tau-protein kinase) inhibitor
hyperforinhyperforin : A cyclic terpene ketone that is a prenylated carbobicyclic acylphloroglucinol derivative produced by St. John's Wort, Hypericum perforatum.

hyperforin: a prenylated acylphloroglucinol derivative; antibiotic component of novoimanine; psychoactive agent in St. John's wort; Russian; structure;
surfactin csurfactin C : A cyclodepsipeptide that is N-[(3R)-3-hydroxy-13-methyltetradecanoyl]-L-alpha-glutamyl-L-leucyl-D-leucyl-L-valyl-L-alpha-aspartyl-D-leucyl-L-leucine in which the C-terminal carboxy group has been lactonised by condensation with the alcoholic hydroxy group.cyclodepsipeptide;
lipopeptide antibiotic;
macrocyclic lactone
antibacterial agent;
antifungal agent;
antineoplastic agent;
antiviral agent;
metabolite;
platelet aggregation inhibitor;
surfactant
resveratroltrans-resveratrol : A resveratrol in which the double bond has E configuration.resveratrolantioxidant;
phytoalexin;
plant metabolite;
quorum sensing inhibitor;
radical scavenger
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
pnu183792PNU183792: structure in first source
CHIC-35CHIC-35 : An organic heterotricyclic compound resulting from the formal fusion of the 2-3 bond of 5-chloroindole with the 2-3 bond of cycloheptanecarboxamide (the S enantiomer). It is a potent, cell-permeable, metabolically stable and selective inhibitor of the deacetylase SIRT1.aromatic compound;
organic heterotricyclic compound;
organochlorine compound;
primary carboxamide
EC 3.5.1.98 (histone deacetylase) inhibitor
1-(3,4-dichlorophenyl)-3-(5-pyridin-4-yl-1,3,4-thiadiazol-2-yl)ureaureas
3-(1-azepanylsulfonyl)-n-(3-bromphenyl)benzamide3-(1-azepanylsulfonyl)-N-(3-bromphenyl)benzamide: a sirtuin 2 inhibitor; structure in first source
CAY10591CAY10591: a SIRT1 NAD-dependent histone deacetylase activatorquinoxaline derivative
sirtinolaldimine;
benzamides;
naphthols
anti-inflammatory agent;
EC 3.5.1.98 (histone deacetylase) inhibitor;
Sir2 inhibitor
cambinolcambinol: inhibitor of human silent information regulator 2 enzymes; structure in first source
(4-chlorophenyl)-[4-(8-nitro-5-quinolinyl)-1-piperazinyl]methanoneN-arylpiperazine
ex 5276-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide : A member of the class of carbazoles that is 2,3,4,9-tetrahydro-1H-carbazole which is substituted at position 1 by an aminocarbohyl group and at position 6 by a chlorine.

6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide: structure in first source
carbazoles;
monocarboxylic acid amide;
organochlorine compound
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
panobinostatpanobinostat : A hydroxamic acid obtained by formal condensation of the carboxy group of (2E)-3-[4-({[2-(2-methylindol-3-yl)ethyl]amino}methyl)phenyl]prop-2-enoic acid with the amino group of hydroxylamine. A histone deacetylase inhibitor used (as its lactate salt) in combination with bortezomib and dexamethasone for the treatment of multiple myeloma.

Panobinostat: An indole and hydroxamic acid derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used as an antineoplastic agent in combination with BORTEZOMIB and DEXAMETHASONE for the treatment of MULTIPLE MYELOMA.
cinnamamides;
hydroxamic acid;
methylindole;
secondary amino compound
angiogenesis modulating agent;
antineoplastic agent;
EC 3.5.1.98 (histone deacetylase) inhibitor
1-aminoadenosine1-aminoadenosine: structure
oblongifolin coblongifolin C: has antineoplastic activity; isolated from Garcinia yunnanensis; structure in first source
3-o-methylfunicone3-O-methylfunicone: derived from Penicillium pinophilum; structure in first source
quisinostatindoles
sch 725680Sch 725680: an aazaphilone from Aspergillus sp.; structure in first source
srt1460SRT1460: small molecule activator of SIRT1 as therapeutics for the treatment of type 2 diabetes; structure in first source
srt1720
srt2183SRT2183: small molecule activator of SIRT1 as therapeutics for the treatment of type 2 diabetes; structure in first source
tenovin-6tenovin-6 : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 5-(dimethylamino)pentanoic acid with the aromatic amino group of N-[(4-aminophenyl)carbamothioyl]-4-tert-butylbenzamide.monocarboxylic acid amide;
tertiary amino compound;
thioureas
antineoplastic agent;
p53 activator;
Sir2 inhibitor
1-[4-fluoro-3-(trifluoromethyl)phenyl]-3-(5-pyridin-4-yl-1,3,4-thiadiazol-2-yl)ureaureas
acy-1215ricolinostat: an HDAC6 inhibitor; structure in first sourcepyrimidinecarboxylic acid
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
pinophilin bpinophilin B: from cultures of a fungus (Penicillium pinophilum Hedgcok) derived from a seaweed; structure in first source
aristoforinAristoforin: derivative of hyperforin, is a potent anticancer agent; structure in first source
n(2)-(4-n-butylphenyl) 2'-deoxyguanosineN(2)-(4-n-butylphenyl) 2'-deoxyguanosine: RN & structure given in first source
n-(3-((2-hydroxynaphthalen-1-ylmethylene)amino)phenyl)-2-phenylpropionamide