Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ether-permeabilized (nucleotide-permeable) Escherichia coli cells exhibited DNA excision repair when exposed to the following carcinogenic K-region epoxides: 7-methyl- and 7,12-dimethyl-benz[a]anthracene-5,6-oxide, chrysene-5,6-oxide and benzo[a]pyrene-4,5-oxide. This DNA excision repair was missing in uvr A and uvr B mutant cells. The K-region epoxide phenanthrene-9,10-oxide was ineffective in all E. coli strains tested. In contrast to the K-region epoxides which where found active only in wild type cells, 1,2,3,4-diepoxybutane and the 6,7-epoxides of the tumor promoter TPA (12-O-tetradecanoyl-phorbol-13-acetate) elicited DNA repair in uvrA, uvrB mutant cells as well. Enzymic activities catalyzing particular repair steps were identified by determining a) repair polymerization and b) size reduction of denatured DNA. A) An easily quantifiable effect in E. coli wild type cells was epoxide-induced repair polymerization. None of the K-region epoxides tested stimulated DNA repair synthesis in uvrA, uvrB mutant cells, indicating that the uvrA-, uvrB-controlled UV-endonuclease initiated excision repair by cleaving epoxide-damaged DNA. 1,2,3,4-Diepoxybutane and the TPA-6,7-oxides induced DNA repair polymerization in uvr-deficient cells, although to a lesser extent than in wild type cells, suggesting the involvement of uvr-independent incision steps. None of the epoxides induced repair polymerization in a mutant (polA107) lacking the 5'--3'exonucleolytic activity of DNA polymerase I (exonuclease VI). The absence of any repair polymerization in the polA107 mutant indicates that the exonuclease VI plays a central role in removing epoxide-damaged nucleotides. As evidenced by greatly reduced levels of repair polymerization measured in polA1 cells, DNA polymerase I was the main polymerizing enzyme. b) As a consequence of treatment with 7-methyl-benz[a]anthracene-5,6-oxide, DNA from wild type cells, contrary to uvrA mutant cells, showed size reduction after denaturation and sedimentation in alkaline sucrose gradients. This is explained by repair-specific endonucleolytic cleavage of damaged DNA. The incision required the presence of ATP indicating that functional UV-endonuclease needs ATP as a cofactor.
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PMID:Carcinogen-induced DNA repair in nucleotide-permeable Escherichia coli cells. Analysis of DNA repair induced by carcinogenic K-region epoxides and 1,2,3,4-diepoxybutane. 15 97

Pseudomonas fluorescens strain LP6a, isolated from petroleum condensate-contaminated soil, utilizes the polycyclic aromatic hydrocarbons (PAHs) naphthalene, phenanthrene, anthracene and 2-methylnaphthalene as sole carbon and energy sources. The isolate also co-metabolically transforms a suite of PAHs and heterocycles including fluorene, biphenyl, acenaphthene, 1-methylnaphthalene, indole, benzothiophene, dibenzothiophene and dibenzofuran, producing a variety of oxidized metabolites. A 63 kb plasmid (pLP6a) carries genes encoding enzymes necessary for the PAH-degrading phenotype of P. fluorescens LP6a. This plasmid hybridizes to the classical naphthalene degradative plasmids NAH7 and pWW60, but has different restriction endonuclease patterns. In contrast, plasmid pLP6a failed to hybridize to plasmids isolated from several phenanthrene-utilizing strains which cannot utilize naphthalene. Plasmid pLP6a exhibits reproducible spontaneous deletions of a 38 kb region containing the degradative genes. Two gene clusters corresponding to the archetypal naphthalene degradation upper and lower pathway operons, separated by a cryptic region of 18 kb, were defined by transposon mutagenesis. Gas chromatographic-mass spectrometric analysis of metabolites accumulated by selected transposon mutants indicates that the degradative enzymes encoded by genes on pLP6a have a broad specificity permitting the oxidation of a suite of polycyclic aromatic and heterocyclic substrates.
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PMID:Transposon and spontaneous deletion mutants of plasmid-borne genes encoding polycyclic aromatic hydrocarbon degradation by a strain of Pseudomonas fluorescens. 898 93

The building of robust and versatile inorganic scaffolds with artificial metallo-nuclease (AMN) activity is an important goal for bioinorganic, biotechnology, and metallodrug research fields. Here, a new type of AMN combining a tris-(2-pyridylmethyl)amine (TPMA) scaffold with the copper(II) N,N'-phenanthrene chemical nuclease core is reported. In designing these complexes, the stabilization and flexibility of TPMA together with the prominent chemical nuclease activity of copper 1,10-phenanthroline (Phen) were targeted. A second aspect was the opportunity to introduce designer phenazine DNA intercalators (e.g., dipyridophenazine; DPPZ) for improved DNA recognition. Five compounds of formula [Cu(TPMA)(N,N')]2+ (where N,N' is 2,2-bipyridine (Bipy), Phen, 1,10-phenanthroline-5,6-dione (PD), dipyridoquinoxaline (DPQ), or dipyridophenazine (DPPZ)) were developed and characterized by X-ray crystallography. Solution stabilities were studied by continuous-wave EPR (cw-EPR), hyperfine sublevel correlation (HYSCORE), and Davies electron-nuclear double resonance (ENDOR) spectroscopies, which demonstrated preferred geometries in which phenanthrene ligands were coordinated to the copper(II) TPMA core. Complexes with Phen, DPQ, and DPPZ ligands possessed enhanced DNA binding activity, with DPQ and DPPZ compounds showing excellent intercalative effects. These complexes are effective AMNs and analysis with spin-trapping scavengers of reactive oxygen species and DNA repair enzymes with glycosylase/endonuclease activity demonstrated a distinctive DNA oxidation activity compared to classical Sigman- and Fenton-type reagents.
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PMID:Polypyridyl-Based Copper Phenanthrene Complexes: A New Type of Stabilized Artificial Chemical Nuclease. 3022 2