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DNA replication proofreading

Definition

Target type: biologicalprocess

Correction of replication errors by DNA polymerase using a 3'-5' exonuclease activity. [GOC:ai]

DNA replication proofreading is a crucial process that ensures the fidelity of DNA replication, minimizing errors and preserving the integrity of the genetic code. It involves a series of steps executed by specialized enzymes, primarily DNA polymerases, to detect and correct mismatched nucleotides during DNA synthesis.

The process begins with the incorporation of a nucleotide by DNA polymerase during the elongation phase of DNA replication. If a mismatched nucleotide is incorporated, the polymerase's active site, which usually has a high affinity for correct base pairing, will recognize the mismatch due to its altered geometry and destabilized hydrogen bonding. This recognition triggers a proofreading mechanism.

The DNA polymerase then utilizes its 3' to 5' exonuclease activity. This activity acts like a "backspace" key, allowing the enzyme to remove the newly incorporated mismatched nucleotide from the 3' end of the newly synthesized strand. Once the mismatched nucleotide is excised, the polymerase can then insert the correct nucleotide, restoring the accurate base pairing.

The exonuclease activity of DNA polymerases is highly specific for mismatched nucleotides, ensuring that only incorrect bases are removed. This specificity is crucial for maintaining the fidelity of replication and preventing the accumulation of mutations.

In summary, DNA replication proofreading involves a complex interplay of enzymatic activities, including the ability to detect mismatches, excise incorrect nucleotides, and incorporate the correct bases. This process is essential for maintaining the integrity of the genome and preventing the propagation of mutations, ensuring the proper functioning of cells and the inheritance of genetic information.'
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Proteins (3)

ProteinDefinitionTaxonomy
Ribonuclease TA ribonuclease T that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P30014]Escherichia coli K-12
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)
DNA polymerase subunit gamma-1A DNA polymerase subunit gamma-1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P54098]Homo sapiens (human)

Compounds (15)

CompoundDefinitionClassesRoles
citric acid, anhydrouscitric acid : A tricarboxylic acid that is propane-1,2,3-tricarboxylic acid bearing a hydroxy substituent at position 2. It is an important metabolite in the pathway of all aerobic organisms.

Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability.
tricarboxylic acidantimicrobial agent;
chelator;
food acidity regulator;
fundamental metabolite
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
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
dithionitrobenzoic aciddithionitrobenzoic acid : An organic disulfide that results from the formal oxidative dimerisation of 2-nitro-5-thiobenzoic acid. An indicator used to quantify the number or concentration of thiol groups.

Dithionitrobenzoic Acid: A standard reagent for the determination of reactive sulfhydryl groups by absorbance measurements. It is used primarily for the determination of sulfhydryl and disulfide groups in proteins. The color produced is due to the formation of a thio anion, 3-carboxyl-4-nitrothiophenolate.
nitrobenzoic acid;
organic disulfide
indicator
ochracinochracin: produced by Aspergillus alutaceus; structure in first sourceisochromanes
zidovudine triphosphate
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
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
pecilocinpecilocin: fungicidal antibiotic produced by Paecilomyces varioti Bainier var. antibioticus; structureN-acylpyrrolidine
sch 725680Sch 725680: an aazaphilone from Aspergillus sp.; structure in first source
pinophilin bpinophilin B: from cultures of a fungus (Penicillium pinophilum Hedgcok) derived from a seaweed; structure in first source
deoxyguanosine triphosphatedeoxyguanosine phosphate;
guanyl deoxyribonucleotide;
purine 2'-deoxyribonucleoside 5'-triphosphate
Arabidopsis thaliana metabolite;
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
plant metabolite;
Saccharomyces cerevisiae metabolite
acyclovir triphosphate