Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.1.1.37 (DNA methyltransferase)
4,983 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over 20% of the cytosine bases in frog virus 3 DNA are methylated at the 5-carbon position. To determine whether this high degree of methylation is the result of a virus-specific enzyme, we examined the kinetics of induction and the substrate specificity of a DNA methyltransferase from frog virus 3-infected fathead minnow cells. A novel DNA methyltransferase activity appeared in the cytoplasm of infected cells at 3 h postinfection. This activity was induced in the absence of viral DNA replication and was therefore probably an early viral enzyme. In contrast to the methyltransferase activity extracted from uninfected cell nuclei, the cytoplasmic enzyme showed a strong template preference for double-stranded over single-stranded and for unmethylated over hemimethylated DNA. The dinucleotide sequence dCpdG was a necessary and sufficient exogenous substrate for methylation in vitro. A mutant of frog virus 3, isolated as resistant to 5-azacytidine and having unmethylated virion DNA, did not induce cytoplasmic DNA methyltransferase, leading to the conclusion that this activity is coded for by the virus.
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PMID:DNA methyltransferase induced by frog virus 3. 669 Jul 23

O6-Methylguanine-DNA methyltransferase activity was measured in extracts of human tumor cells and was partially purified from human placenta. Repair of O6-methylguanine in DNA inactivated the methyltransferase, and treatment of cells with MNNG, which produces this alkylated base in DNA, depleted the cells of active methyltransferase. RNA and protein synthesis were required for restoration of methyltransferase activity, which transiently exceeded the original levels by 50% 48 h after treatment. One species of methyltransferase of Mr = 22 kd was present in human tumor cells and human placenta.
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PMID:O6-Methylguanine-DNA methyltransferase in human cells. 669 57

O6-Methylguanine-DNA methyltransferase activity, i.e., the capacity of cells to transfer the methyl group from O6-methylguanine in DNA to protein, was determined in 10 hepatoma cell lines, all derived from Reuber H35 hepatoma but differing in their status of differentiation. Methyltransferase activity of the six differentiated lines tested was at least 4-5 times higher than that of two dedifferentiated lines. The activity of the two poorly differentiated lines examined was low to intermediate. Some of the differentiated lines possessed methyltransferase activities comparable to those in hepatocytes freshly isolated from adult rat. The results suggest that certain differentiated hepatoma lines are capable of mimicking liver in the capacity for repair of O6-methylguanine lesions and in this respect may be useful as model systems for studying liver-specific effects of monofunctional alkylating agents.
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PMID:The capacity of rat hepatoma cell lines for O6-methylguanine-DNA repair correlates with their status of differentiation. 673 58

The phage Mu mom gene controls an unusual DNA modification. Expression of the mom function requires an active host (dam+) DNA adenine methylase [S-adenosyl-L-methionine:DNA (6-aminopurine)-methyltransferase]; in dam- hosts, Mu development is normal except that the viral DNA does not undergo the mom modification. The present communication compares transcription of the mom gene in dam+ versus dam- cells. 32P-labeled probes were prepared by nick-translation of a purified mom gene-containing restriction fragment and of virion DNA, respectively. These probes were hybridized with various RNAs blotted onto nitrocellulose filters (after fractionation by agarose gel electrophoresis). The salient findings are: (i) mom-specific RNA was readily detected in dam+ lysogenic cells, but only after induction of the Mu prophage; (ii) the level of mom RNA was decreased at least to 1/20th in induced dam- Mu lysogens; and (iii) little difference, if any, was observed between dam+ and dam- cells with respect to total Mu transcripts produced after prophage induction. These results are in accord with the known pattern of mom gene expression and Mu development. They show that the host (dam+) DNA adenine methylase activity is required for transcription of the mom gene. This represents a unique example where a DNA methylase exerts a positive regulatory role in mRNA transcription; alternative mechanisms for this process will be discussed.
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PMID:DNA methyltransferase-dependent transcription of the phage Mu mom gene. 675 51

A diverse range of ultimate chemical carcinogens inhibited the transfer of methyl groups from S-adenosylmethionine to hemimethylated DNA in a reaction catalyzed by mouse spleen methyltransferase. The formation of alkali-labile sites in DNA lessened its ability to accept methyl groups in vitro, but the methylation reaction was much less sensitive to thymine dimers or double-strand breaks. Carcinogens induced the formation of alkali-labile DNA lesions, but the degree of methyltransferase inhibition observed was greater than that expected for this damage alone. Certain carcinogens were also capable of direct modification and inactivation of the methyltransferase enzyme. Benzo(a)pyrene treatment of living BALB/3T3 A31 clone 1-13 but not C3H/10T1/2 clone 8 cells resulted in a 12% decrease in total 5-methylcytosine content of cellular DNA. Carcinogenic agents may therefore cause heritable changes in 5-methylcytosine patterns in certain cell types by a variety of mechanisms, including adduct formation, induction of apurinic sites and single-strand breaks and direct inactivation of DNA methyltransferase.
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PMID:Inhibition of DNA methylation by chemical carcinogens in vitro. 682 70

DNA (cytosine-5)-methyltransferases can cause deamination of cytosine when the cofactor S-adenosylmethionine (AdoMet) is limiting and thus function as sequence-specific C-->U mutator enzymes. Here we explored whether mutations causing inactivation of the cofactor binding activity of the HpaII methyltransferase, thus mimicking conditions of limiting AdoMet concentration, could convert a DNA methyltransferase to a C-->U mutator enzyme. We created two mutator enzymes from the HpaII methyltransferase (F38S and G40D) which both showed enhanced cytosine deamination activities in vitro and in vivo. Interestingly, the G:U mispairs generated by these enzymes were not repaired completely in bacteria equipped with uracil-DNA glycosylase-initiated repair machinery, giving rise to a potent mutator phenotype. This is the first report showing the creation of mutator enzymes from a DNA methyltransferase and the demonstration of their mutagenicity in living cells.
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PMID:A mutant HpaII methyltransferase functions as a mutator enzyme. 750 46

Wild-type Vibrio cholerae cells, when adapted by a stepwise treatment with sub-lethal concentrations of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), acquired resistance to killing and mutagenesis by subsequent challenges with higher concentrations of MNNG. This was also seen in the rec isogenic strain indicating that the observed phenomenon was not due to the induction of SOS functions. Further, the adapted cells of both the wild-type and rec strains could reactivate lethally alkylated phages with equal efficiency. Increased resistance of adapted cells correlated with the induction of a 17-kDa DNA methyltransferase, capable of repairing O6-methylguanine lesions in DNA. This induced methyltransferase was found to be antigenically unrelated to the Escherichia coli methyltransferase (Ada protein) as determined by Western blotting with polyclonal antiserum raised against the E. coli protein. Even though no counterpart of the constitutively expressed methyltransferase (Ogt) of E. coli could be detected in V. cholerae, several lines of evidence pointed towards the presence of an E. coli alk A-like gene in the organism.
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PMID:Evidence for a weak adaptive response to alkylation damage in Vibrio cholerae. 752 98

An unusual cluster of tandemly repeated DNA sequences (TRS) was found downstream from the gene encoding DsaV methyltransferase, the DNA modification enzyme in the DsaV restriction-modification system found in a strain of Dactylococcopsis salina (Ds). The repeat unit is about 32-bp long and is present 13 times in the cluster. Each repeat unit can be divided into two distinct parts based on the level of sequence conservation and evolution. Hybridization of Ds DNA with a probe specific for this cluster revealed that there were at least two additional sites within the genome with similar TRS. The TRS units are localized in one region of the Ds genome. They do not share significant sequence similarity with other TRS found in prokaryotes.
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PMID:A novel repetitive sequence lies near the gene encoding a cytosine methyltransferase in the cyanobacterium Dactylococcopsis salina. 759 Mar 24

Limited proteolysis has been used to probe the domain structure of the type I DNA methyltransferase M.EcoR124I. Trypsin digestion of the methyltransferase generates two fragments derived from the HsdS subunit, a 28 kDa N-terminal domain and a 19 kDa C-terminal domain, leaving the HsdM subunit intact. Extensive digestion by chymotrypsin, however, removes 59 amino acid residues from the N terminus of the HsdM subunit to leave a 52 kDa C-terminal domain. Binding of the cofactor S-adenosyl methionine has no appreciable effect on the rate of cleavage, but binding of a 30 bp DNA duplex containing the cognate recognition sequence confers almost total protection. Following trypsin cleavage of the methyltransferase, a stable proteolytic product is produced which has been purified for biochemical characterisation. The trypsinised enzyme is shown to be a multimeric complex containing two intact HsdM subunits and both fragments of the HsdS subunit, consistent with the circular model proposed for the organisation of domains in the specificity subunit in type IC methyltransferases. Gel retardation studies show that the proteolysed enzyme still retains DNA binding activity, but its specificity for the DNA recognition sequence is dramatically reduced.
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PMID:Probing the domain structure of the type IC DNA methyltransferase M.EcoR124I by limited proteolysis. 760 69

Besides modulating specific DNA-protein interactions, methylated cytosine, frequently referred to as the fifth base of the genome, also influences DNA structure, recombination, transposition, repair, transcription, imprinting, and mutagenesis. DNA (cytosine-5-)-methyltransferase catalyzes cytosine methylation in eukaryotes. We have cloned and expressed this enzyme in Escherichia coli, purified it to apparent homogeneity, characterized its properties, and we have shown that it hemimethylates DNA. The cDNA for murine maintenance methyltransferase was reconstructed and cloned for direct expression in native form. Immunoblotting revealed a unique protein (M(r) = 190,000) not present in control cells. The mostly soluble overexpressed protein was purified by DEAE, Sephadex, and DNA cellulose chromatography. Peak methylating activity correlated with methyltransferase immunoblots. The purified enzyme preferentially transferred radioactive methyl moieties to hemimethylated DNA in assays and on autoradiograms. All of the examined properties of the purified recombinant DNA methyltransferase are consistent with the enzyme purified from mammalian cells. Further characterization revealed enhanced in vitro methylation of premethylated oligodeoxynucleotides. The cloning of hemimethyltransferase in E. coli should allow facilitated structure-function mutational analysis of this enzyme, studies of its biological effects in prokaryotes, and potential large scale methyltransferase production for crystallography, and it may have broad applications in maintaining the native methylated state of cloned DNA.
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PMID:Mammalian DNA (cytosine-5-)-methyltransferase expressed in Escherichia coli, purified and characterized. 762 84


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