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

The CHO-UV-1 mutant, a Chinese hamster ovary cell with defective postreplication recovery of DNA, is 2- to 4-fold more sensitive than its wild-type counterpart (CHO-77256) to the lethal effects of ethylating agents and UV radiation; it is also hypersensitive (10- to 20-fold) to some DNA-methylating and -cross-linking agents. We studied the CHO-UV-1 mutant further to define its phenotype in terms of DNA damage induction and repair, methyltransferase activity, and effects of caffeine on mutational and lethal responses. Both wild-type and CHO-UV-1 cells incurred similar levels and types of damage when exposed to UV radiation, N-methyl-N'-nitro-N-nitrosoguanidine, or N-methyl-N-nitrosourea. The rate and extent of repair of Micrococcus luteus endonuclease-sensitive sites after UV irradiation or treatment with N-methyl-N'-nitro-N-nitrosoguanidine were also equivalent in these two cell types. Twenty % of the initial endonuclease-sensitive sites induced in either cell line remained at 18 h after UV irradiation; approximately 8% of the sites after N-methyl-N'-nitro-N-nitrosoguanidine exposure were present in both parental and CHO-UV-1 cells after a 17-h repair period. Moreover, the ability of CHO-UV-1 to resynthesize and ligate DNA during excision repair was similar to that of its parent. Neither CHO-UV-1 nor CHO-77256 had appreciable levels of O6-methylguanine-DNA methyltransferase activity which ameliorates the cytotoxicity of alkylating agents. Caffeine, a known inhibitor of postreplication repair, decreased the frequency of mutation induction at the hypoxanthine-guanine phosphoribosyltransferase locus by 40-55% in CHO-77256 but not in CHO-UV-1. These results rule out defective excision repair as a factor in the hypersensitivity of the CHO-UV-1 mutant to DNA-damaging agents. Hence, this cell line appears to derive from a mutation affecting nonexcision repair processes and should be useful in clarifying the mechanism(s) of postreplication recovery of DNA in mammalian cells.
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PMID:Genetic and biochemical characterization of the CHO-UV-1 mutant defective in postreplication recovery of DNA. 231 21

The mutagenic activity of O6-methylguanine has been investigated using a single-stranded M13mp8 phage DNA molecule in which a single O6-methylguanine residue was positioned in the unique recognition site for the restriction endonuclease, Pst I. After introduction of this vector into Escherichia coli, progeny phage were produced, of which 0.4% were mutated in their Pst I site. To determine the impact of DNA repair on mutagenesis, levels of O6-methylguanine-DNA methyltransferase (an O6-methylguanine repair protein) were depleted in host cells by treatment with N-methyl-N'-nitro-N-nitrosoguanidine prior to viral DNA uptake. In these cells, the mutation frequency due to O6-methylguanine increased with increasing N-methyl-N'-nitro-N-nitrosoguanidine dose (the highest mutation frequency observed was 20%). DNA sequence analysis of mutant genomes revealed that O6-methylguanine induced G to A transitions, exclusively.
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PMID:Mutagenesis and repair of O6-substituted guanines. 353 91

Eukaryotic cells have multiple mechanisms for repairing damaged DNA. O6-methylguanine-DNA methyltransferase directly reverses some simple alkylation adducts. However, most repair strategies excise lesions from DNA. Two major pathways are base excision repair (BER), which eliminates single damaged-base residues, and nucleotide excision repair (NER), which excises damage within oligomers that are 25-32 nucleotides long. The specialized DNA glycosylases and AP endonucleases of BER act on spontaneous and induced DNA alterations caused by hydrolysis, oxygen free radicals, and simple alkylating agents. NER utilizes many proteins (including the XP proteins in humans) to remove the major UV-induced photoproducts from DNA, as well as other types of modified nucleotides. Different DNA polymerases and ligases are used to complete the separate pathways. Some organisms have alternative schemes, which include the use of photolyases and a specific UV-endonuclease for repairing UV damage to DNA. Finally, double-strand breaks in DNA are repaired by mechanisms that involve recombination proteins and, in mammalian cells, a DNA protein kinase.
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PMID:DNA repair in eukaryotes. 881 Nov 77

Only two DNA repair enzymes, DNA polymerase beta and O6-methylguanine-DNA methyltransferase, have been shown to be inducible in mammalian cells by genotoxic agents. We show here that crocidolite asbestos induces the DNA repair enzyme, apurinic/apyrimidinic (AP)-endonuclease, in isolated mesothelial cells, the progenitor cells of malignant mesothelioma. Asbestos at nontoxic concentrations of 1.25 and 2.5 microg/cm2 significantly increased AP-endonuclease mRNA and protein levels as well as enzyme activity (P < 0.05) in a dose-dependent manner in rat pleural mesothelial cells. These increases were persistent from 24 to 72 h after initial exposure to fibers. Changes were not observed with glass beads, a noncarcinogenic particle. Confocal scanning laser microscopy showed that AP-endonuclease was primarily localized in the nucleus but also in mitochondria. Our data are the first to demonstrate the inducibility of AP-endonuclease by a human class I carcinogen associated with oxidant stress in normal cells of the lung.
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PMID:Asbestos increases mammalian AP-endonuclease gene expression, protein levels, and enzyme activity in mesothelial cells. 944 89