Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.22.1 (DNase II)
 429 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bleomycin (BLM) exclusively affects thymidine-containing compounds such as DNA and polydeoxyribonucleotides by releasing free thymine and leaving aldehyde functions. Molecular morphology and base sequence of the DNA strongly influence BLM activity. High BLM concentrations, besides modifying DNA into oligothyminic or athyminic nucleic acids, cause strand scissions. Enzymatic DNA and RNA synthesis is strongly influenced by BLM. The inhibition in DNA-dependent DNA polymerase and DNA-dependent RNA polymerase assays is of the non-competitive type. Protein biosynthesis in in vitro systems is not affected by BLM even at high concentrations. BLM turns out to be a strong inhibitor of DNase I and of DNase II; the inhibition is of the competitive type. The enzymatic activities of nucleases using RNA as substrate (RNase A, RNase B, Rnase T1, venom phosphodiesterase I and spleen phosphodiesterase II) are not influenced by this antibiotic. The antibiotic reduces cell proliferation (L5178y mouse lymphoma cells) in vitro in low concentrations by cytostasis and at higher concentrations by cytotoxicity. In BLM-treated L5178y cells, DNA synthesis is strongly reduced, while RNA and protein synthesis are not affected. In vivo, using growing quail oviducts, cell proliferation and cytodifferentiation are markedly inhibited after BLM treatment. This is attributed to the observed inhibition of DNA synthesis. RNA and protein synthesis as well as gene expression are not influenced by BLM under the conditions used. The selective inhibition of DNA synthesis in vivo may be caused by the following mechanisms: (1) competition of BLM with RNA; (2) blocking of the accessibility of DNA in chromatin to BLM, and (3) dependence from the repair processes. BLM inhibits growth of sarcomas, induced by oncogenic RNA viruses in vivo; well-developed tumours show regression after BLM treatment. Transformation of chick embryo fibroblasts by oncogenic RNA viruses in vitro and growth of these viruses is blocked by BLM; the most sensitive period for BLM inhibition is the time during the first period (integration of viral genome into cellular genome?) after infection.
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PMID:Effect of bleomycin on DNA, RNA, protein, chromatin and on cell transformation by oncogenic RNA viruses. 6 69

Though DNase does not contain any cysteine residues, incubation of the enzyme with 2-nitro-5-thiocyanobenzoic acid in the presence of Ca2+ at pH values above 7.5 results in an irreversible inactivation of the enzyme. The inactivation also occurs when Ca2+ is replaced by Mg2+, but not in their absence. Amino acid analyses after acid hydrolyses of the completely inactivated ant the native enzymes show no significant differences in composition, including tryptophan and half-cystine residues. However, sodium dodecyl sulfate gel electrophoresis indicates enzyme cleavage by the treatment with 2-nitro-5-thiocyanobenzoic acid. This reagent does not inactivate chymotrypsin and lysozyme, and under conditions where bovine DNase is inactivated, does not inactivate other nucleases such as ribonuclease, snake venom phosphodiesterase, and spleen acid DNase. However, it inactivates malt DNase and can, therefore, be considered a specific inhibitor of DNase I. The inactivation kinetics is pseudo-first order, resembling Michaelis-Menten, with an affinity constant of 16.7 mM. It is the cyano group, not the thionitrobenzoic acid of 2-nitro-5-thiocyanobenzoic acid that reacts to form cyano-DNase.
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PMID:Inactivation of bovine pancreatic DNase by 2-nitro-5-thiocyanobenzoic acid. I. A novel inhibitor for DNase I. 48 54

The following procedures have been used to prepare fifteen modified dinucleoside monophosphates: (a) bisulfite-catalyzed transamination with aniline to give an N4-phenylcytidine (CPh), (b) bisulfite-catalyzed transamination with beta-naphthylamine to give an N4-beta-naphthylcytidine (CbetaN), (c) alkylation with 7-bromomethylbenz[a] anthracene to afford a 7(benz[a]anthryl-7-methyl)guanosine (GMBA), and (d) reaction with N-acetoxy-2-acetylaminofluorene to give an 8-(N-2-fluorenylacetamido)guanosine (GAAF). The compounds prepared were A-CPh, CPh-A, CPh-G, U-CPh, CPh-U, A-CbetaN, CbetaN-A, G-CbetaN, CbetaN-G, U-CbetaN, CbetaN-U, GMBA-U, U-GMBA, GAAF-U, and U-GAAF. All of the modified compounds were hydrolyzed to the expected monomers with venom and spleen exonucleases. Hydrolysis by micrococcal nuclease was inhibited in the following cases: A-CPh, A-CbetaN, U-GMBA, and U-GAAF. The first three reactions above were applied to denatured calf thymus DNA to prepare modified DNA samples containing from 0.3 to 2.0% bound aromatic residues. The modified nucleic acids were completely hydrolyzed to nucleosides by the combination of venom exonuclease, deoxyribonuclease I and alkaline phosphatase. The same results were obtained with a combination of spleen exonuclease, deoxyribonuclease II, and alkaline phosphatase. Hydrolysis of the modified nucleic acids by micrococcal nuclease and alkaline phosphatase afforded primarily nucleosides, with some dinucleoside monophosphates. The amount of the latter did not exceed that found in the hydrolysis of control DNA, however. Other workers have observed inhibition of enzymatic hydrolysis of nucleic acids modified by aromatic carcinogens. We postulated that their results may have been caused by cross-links, which were avoided in our studies.
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PMID:Preparation and enzymatic hydrolysis of dinucleoside monophosphates and DNA modified with aromatic residues. 55 43