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

---

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

The effect of 3-alkyl substituted imidazotetrazinones on methylation of DNA has been studied in drug sensitive and resistant cell lines. The 3-methyl analogue (Temozolomide) has been shown to cause a decrease in the level of 5-methylcytosine in newly synthesized DNA in both cell lines, although the effect occurred at lower drug concentrations in the drug sensitive cell line. In order to investigate the mechanism of hypomethylation of DNA, calf thymus DNA was alkylated in vitro by both Temozolomide and the 3-ethyl analogue, CCRG 82019, and the alkylated DNA was shown to inhibit the transfer of methyl groups from S-adenosyl-L-methionine to M. lysodeikticus DNA by purified eukaryotic DNA methylase. Neither free drug alone or unmodified DNA affected the methylase reaction. Calf thymus DNA modified with CCRG 82019 was more effective as a methylase inhibitor than DNA modified with Temozolomide, which was a reverse of the order of potencies of the free drugs against tumour cells in culture. CCRG 82019 modified DNA also formed a more stable complex with nuclear proteins. Alterations in the level of 5-methylcytosine in DNA may be important in the alteration of gene expression by these agents.
...
PMID:Antitumour imidazotetrazines and gene expression. 320 8

An Escherichia coli virus T1-induced DNA methyltransferase was identified by activity gel analysis in homogenates of infected E. coli DNA-adenine-methylation-deficient strains. Although the Mr of this protein (31,000) is in the same range as that of the E. coli DNA adenine methyltransferase, the two proteins are not closely related; the E. coli dam gene does not hybridize with T1 DNA. Selective conditions for measurement of the T1 activity were developed, and the enzyme was purified to functional homogeneity, as shown by activity analysis in polyacrylamide gels. Requirements for optimal activity of the viral enzyme were determined to be pH 6.9, ionic strengths below 0.1 M KCl, and a temperature between 40 and 43 degrees C. The Km for S-adenosyl-L-methionine is 4.9 microM. The purified T1 DNA methyltransferase is capable of methylating adenine in 5'-GATC-3' sites in vitro.
...
PMID:Identification, purification, and characterization of Escherichia coli virus T1 DNA methyltransferase. 331 2

5'-Deoxy-5'-(methylthio)adenosine (MTA) alone and in combination with methionine was found to increase frequencies of background HGPRT mutation and SCE in V79 Chinese hamster cells. The same agents exert a comutagenic action on these effects as well as upon mutation induction in Escherichia coli stain AB1157 (but not in its non-adaptable derivative ada-6) following treatment with N-methyl-N-nitrosourea (MNU). MTA plus methionine also enhanced the lethal action of MNU on hamster cells. The effects observed may tentatively be ascribed to hypomethylation due to inhibition of DNA methylase by MTA.
...
PMID:Mutagenic and comutagenic action of 5'-deoxy-5'-(methylthio)adenosine. 351 30

In extracts of E. coli treated with an adapting regime of MNNG, the induced 39kd Ada protein having O6-MeG-DNA methyltransferase activity is processed to a 19kd active domain corresponding to the C-terminal half of the intact protein. This proteolytic processing has been followed on Western immunoblots using antisera raised against the 19kd fragment. Initial processing at 25 degrees C or 37 degrees C mainly generates a fragment of mol. wt. 24kd which then undergoes a slower second cleavage to generate the 19kd active domain. Preceding this second cleavage site is a sequence of amino acids Thr- -Gly-Met-Thr- -Lys that also occurs at another site in the N-terminal half of the 39kd methyltransferase. It is proposed that this sequence is a recognition site for proteolytic activity. On the basis of cleavage of the Ada protein at either one or both of these sites, fragments may be generated of mol. wt. 24kd and 19kd containing the active site for O6-methylguanine and O4-methylthymine repair, and 15kd and 20kd, containing the active site for methylphosphotriester repair. These observations explain previous reports by others on the existence in cell extracts of multiple methyltransferase activities of different sizes recognizing O-methyl lesions in DNA. The cellular protease involved is resistant to a wide range of protease inhibitors.
...
PMID:Proteolytic processing of the Ada protein that repairs DNA O6-methylguanine residues in E. coli. 354 5

The activity of eukaryotic DNA methyltransferase diminishes with time when the enzyme is incubated with high concentrations (200-300 micrograms/ml) of unmethylated double-stranded Micrococcus luteus DNA. Under similar conditions, single-stranded DNA induces only a limited decrease of enzyme activity. The inactivation process is apparently due to a slowly progressive interaction of the enzyme with double-stranded DNA that is independent of the presence of S-adenosyl-L-methionine. The inhibited enzyme cannot be reactivated either by high salt dissociation of the DNA-enzyme complex or by extensive digestion of the DNA. Among synthetic polydeoxyribonucleotides both poly(dG-dC).poly(dG-dC) and poly(dA-dT).poly(dA-dT), but not poly(dI-dC).poly(dI-dC), cause inactivation of DNA methyltransferase. This inactivation process may be of interest in regulating the 'de novo' activity of the enzyme.
...
PMID:Inactivation of de novo DNA methyltransferase activity by high concentrations of double-stranded DNA. 367 27

Previously, we have derived murine hybridomas producing monoclonal antibodies against DNA methyltransferase from human placenta (Kaul, S., Pfeifer, G. P., and Drahovsky, D. (1984) Eur. J. Cell Biol. 34, 330-335). One of these monoclonal antibodies, M2B10, which undergoes immune complex formation also with DNA methyltransferase from P815 mouse mastocytoma cells, was used for the immunoaffinity purification of mouse and human DNA methyltransferases. In sodium dodecyl sulfate-polyacrylamide gels and in immunoblotting studies, the immunoaffinity-purified mouse DNA methyltransferase revealed 5-6 polypeptides of molecular masses 150-190 kDa. The immunoaffinity-purified human placental DNA methyltransferase was characterized by a polypeptide of 158 kDa, presumably representing the native enzyme molecule and by polypeptides of 105-108 kDa and 50-68 kDa, probably generated by a limited proteolysis of the native enzyme molecule. The immunoaffinity-purified DNA methyltransferases preferred hemimethylated DNA substrates over unmethylated ones, and among all unmethylated substrates tested, poly[(dG-dC).(dG-dC)] had the highest methyl-accepting activity. DNA polymers of at least 90 base pairs in length were required for the binding reaction of the immunoaffinity-purified human DNA methyltransferase, and this initial binding was apparently independent of the nucleotide composition of the DNA polymer and of the presence of S-adenosyl-L-methionine.
...
PMID:Purification and characterization of mammalian DNA methyltransferases by use of monoclonal antibodies. 393 45

An express method for measuring the level of in vitro DNA methylation in homogenates and nuclei from animal tissues as well as during initial steps of DNA methylase isolation and purification when methylase activity is low and hardly testable by other methods has been suggested. The method is based on the measuring the radioactivity incorporated in filter adsorbed DNA (acid-insoluble material) 3H-label from S-adenosile-L-methionine as a result of in vitro DNA methylation. The advantage of the method consists in the replacement of a long-duration repeated deproteinization procedure traditionally used by a relatively simple procedure (15 min incubation of the mixture at 80 degrees C with 10 volumes of the 8M urea, 5 mM EDTA, 5% n-butanol, 2% sodium dodecilsulfate, 1 M sodium chloride solution) and the absence of any loss of DNA. The method is fit for the fast serial assay of DNA methylase activity taking into consideration that about one third of the total acid-insoluble radioactivity is due to the radioactivity in 5-methylcytosine residues in DNA.
...
PMID:[Determination of DNA methylase activity in animal tissue extracts]. 398 46

The N-3 drug resistance (R) factor specifies a deoxyribonucleic acid (DNA)-cytosine methylase and a DNA restriction-modification (hspII) system. We have isolated three independent mutants that are conditionally defective in their ability to modify bacteriophage lambda and to methylate DNA-cytosine residues. The ratio of 5-methylcytosine to N(6)-methyladenine in bacterial DNA and in the DNA of phages lambda and fd was determined after labeling with [methyl-(3)H]methionine at various growth temperatures. Although the ability of the wild-type N-3 factor to modify phage lambda and to methylate DNA-cytosine residues was unaffected with increasing temperature, two of the mutants exhibited a parallel loss in modification and cytosine methylation ability. The ability of the third mutant to carry out these functions was dependent on the presence or absence of an amber suppressor mutation in the host genome. These results offer further support for the notion that hspII modification is mediated by a DNA-cytosine methylase. Evidence is also presented that the modification methylase is responsible for the in vivo methylation of phage fd DNA (which is not subject to hspII restriction in vivo).
...
PMID:Mutants of the N-3 R-factor conditionally defective in hspII modification and deoxyribonucleic acid-cytosine methylase activity. 437 29

The restriction endonuclease from E. coli B is both an endonuclease and a DNA methylase. Both activities either require or are stimulated by Mg(+2), adenosine triphosphate, and S-adenosyl-L-methionine. The particular activity which the enzyme exhibits depends upon the nature of the SB sites, the genetic sites that identify substrate DNA. Enzymatic treatment of DNA that has an unmodified, wild-type SB site results in either rapid restriction of the DNA or very slow methylation of the SB site. On the other hand, a hybrid SB site (modified), which protects the DNA molecule from restriction, results in rapid methylation of that SB site.
...
PMID:Kinetics of methylation of DNA by a restriction endonuclease from Escherichia coli B. 461 May 61

The relationship between antineoplastic activity of 5-aza-2'-deoxycytidine (5-aza-dCyd) in mice with L1210 leukemia and inhibition of DNA methylation was investigated. BALB/c X DBA/2 F1 mice with L1210 leukemia were given a 15-hr i.v. infusion of 5-aza-dCyd at a total dose ranging from 0.5 mg/kg (weak antineoplastic effect) to 22 mg/kg (very potent antineoplastic effect). The DNA of L1210 leukemia cells was isolated from 5-aza-dCyd-treated mice and tested for its ability to accept methyl groups from S-adenosyl-L-methionine in a reaction catalyzed by DNA methyltransferase. The methyl-accepting ability of leukemia cell DNA was found to be dependent on the dose of 5-aza-dCyd, suggesting that this therapy induced significant changes in the level of methylation of the DNA. At the start of the 5-aza-dCyd infusion, mice were given i.p. injections of [6-3H]uridine, and the DNA of the L1210 leukemia cells was isolated at the end of therapy. Analysis of the labeled pyrimidine bases showed that 5-aza-dCyd produced a dose-dependent reduction in the 5-methylcytosine content of the DNA. Thus, there appears to be a correlation between the antileukemic activity of 5-aza-dCyd and its ability to inhibit DNA methylation.
...
PMID:Inhibition of DNA methylation in L1210 leukemic cells by 5-aza-2'-deoxycytidine as a possible mechanism of chemotherapeutic action. 619 May 53


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---