Page last updated: 2024-10-24

3'-5'-DNA exonuclease activity

Definition

Target type: molecularfunction

Catalysis of the sequential cleavage of mononucleotides from a free 3' terminus of a DNA molecule. [GOC:mah]

3'-5'-DNA exonuclease activity refers to the enzymatic process of removing nucleotides from the 3' end of a DNA strand. This activity is crucial for various cellular processes, including DNA repair, replication, and recombination. The enzyme responsible for this activity is known as a 3'-5'-DNA exonuclease.

**Mechanism of Action:**

3'-5'-DNA exonuclease activity involves a series of steps:

1. **Binding:** The exonuclease enzyme binds to the 3' end of the DNA strand.
2. **Hydrolysis:** The enzyme catalyzes the hydrolysis of the phosphodiester bond between the 3' hydroxyl group of the penultimate nucleotide and the 5' phosphate group of the terminal nucleotide.
3. **Nucleotide Release:** The cleaved nucleotide is released from the DNA strand.
4. **Translocation:** The exonuclease enzyme then translocates to the next nucleotide, repeating the process until the desired number of nucleotides have been removed.

**Biological Significance:**

3'-5'-DNA exonuclease activity plays a critical role in maintaining the integrity of the genome. It is essential for:

* **DNA Repair:** Removing damaged or mismatched nucleotides during DNA repair pathways.
* **DNA Replication:** Processing Okazaki fragments during lagging strand synthesis.
* **Recombination:** Excising damaged DNA segments during homologous recombination.
* **Regulation of Gene Expression:** Removing specific nucleotides from DNA sequences to regulate gene expression.

**Examples of 3'-5'-DNA Exonucleases:**

* **DNA Polymerase I:** Possesses 3'-5'-exonuclease activity, which is used for proofreading during DNA replication.
* **Exonuclease I:** A dedicated 3'-5'-exonuclease involved in DNA repair and recombination.
* **RecBCD:** A complex with 3'-5'-exonuclease activity that plays a role in homologous recombination.

**Clinical Relevance:**

Defects in 3'-5'-DNA exonuclease activity can lead to various genetic disorders, including:

* **Bloom Syndrome:** A rare genetic disease characterized by an increased risk of cancer.
* **Xeroderma Pigmentosum:** A disorder characterized by extreme sensitivity to sunlight and an increased risk of skin cancer.
* **Ataxia Telangiectasia:** A neurodegenerative disorder with an increased risk of cancer.

**Conclusion:**

3'-5'-DNA exonuclease activity is a fundamental enzymatic process that plays a vital role in maintaining genome stability and regulating gene expression. Its importance in various cellular processes highlights its significance for human health.'
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Proteins (2)

ProteinDefinitionTaxonomy
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-(apurinic or apyrimidinic site) endonucleaseA DNA-(apurinic or apyrimidinic site) endonuclease that is encoded in the genome of human. [PRO:DNx, UniProtKB:P27695]Homo sapiens (human)

Compounds (25)

CompoundDefinitionClassesRoles
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
hycanthonehycanthone : 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.
thioxanthenesmutagen;
schistosomicide drug
lucanthonelucanthone : 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)
thioxanthenesadjuvant;
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
ochracinochracin: produced by Aspergillus alutaceus; structure in first sourceisochromanes
mitoxantrone hydrochloridehydrochlorideantineoplastic agent
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
3,3',4,4',5,5'-hexabromobiphenyl
6-hydroxydopa6-hydroxydopa: RN given refers to cpd without isomeric designationnon-proteinogenic alpha-amino acid
tanshinone ii atashinone IIA: a cardiovascular agent with antineoplastic activity; isolated from Salvia miltiorrhiza; structure in first sourceabietane diterpenoid
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
1,3,6-trimethylpyrimido[5,4-e][1,2,4]triazine-5,7-dionepyrimidotriazine
pnu183792PNU183792: structure in first source
2-[[5-(dimethylsulfamoyl)-1H-indol-3-yl]methylidene]propanedioic acid diethyl esterindoles
1,6-dimethyl-3-propylpyrimido[5,4-e][1,2,4]triazine-5,7-dionepyrimidotriazine
myricetin7-hydroxyflavonol;
hexahydroxyflavone
antineoplastic agent;
antioxidant;
cyclooxygenase 1 inhibitor;
food component;
geroprotector;
hypoglycemic agent;
plant metabolite
pecilocinpecilocin: fungicidal antibiotic produced by Paecilomyces varioti Bainier var. antibioticus; structureN-acylpyrrolidine
ag 538AG 538: an IGF-1 receptor kinase inhibitor; structure in first source
e 3330E 3330: structure given in first source; MW 378.47
sch 725680Sch 725680: an aazaphilone from Aspergillus sp.; structure in first source
N-[3-(1,3-benzothiazol-2-yl)-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl]acetamidebenzothiazoles
pinophilin bpinophilin B: from cultures of a fungus (Penicillium pinophilum Hedgcok) derived from a seaweed; structure in first source
thiolactomycinthiolactomycin: from actinomycetes; structure given in first source
galloflavingalloflavin: structure in first source