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)

The nonrestricting/nonmodifying strain Bacillus subtilis 222 (r-m-) can be induced to synthesize a DNA-modifying activity upon treatment with either mitomycin C (MC) or UV light. This is shown by the following facts. (i) Infection of MC-pretreated 222 cells with unmodified SPP1 phage yields about 3% modified phage that are resistant to restriction in B. subtilis R (r+m+). The induced modifying activity causes the production of a small fraction of fully modified phage in a minority class of MC-treated host cells. (ii) The MC-pretreated host cells contain a DNA cytosine methylating activity: both bacterial and phage DNAs have elevated levels of 5-methylcytosine. (iii) The MC-induced methylation of SPP1 DNA takes place at the recognition nucleotide sequences of restriction endonuclease R from B. subtilis R. (iv) Crude extracts of MC-pretreated 222 cells have enhanced DNA methyltransferase activities, with a substrate specificity similar to that found in modification enzymes present in (constitutively) modifying strains.
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PMID:Restriction and modification in Bacillus subtilis: inducibility of a DNA methylating activity in nonmodifying cells. 82 59

(Deoxyribonucleic acid from Micrococcus luteus was methylated in vitro in the presence of S-adenosyl-(14C methyl)methionine with a DNA methyltransferase purified from extracts of te. coli infected with bacteriophage T2. The labelled DNA was degraded by enzymatic and specific chemical methods and the resulting short oligonucleotides were separated and characterized. tthe analytical data permit the conclusion that the tdna transmethylase reacts specifically with N-G-A-T-C-N sequences in which it converts adenine to a 6-methyl-aminopurine residue.
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PMID:Specificity of deoxyribonucleic acid transmethylase induced by bacteriophage T2. I. Nucleotide sequences isolated from tmicrococcus luteus DNA methylated in vitro. 110 Dec 23

The effects of dietary selenium deficiency and excess on N-nitrosomethylbenzylamine-(NMBA) induced esophageal neoplasia in rats and forestomach tumors in mice and the effects of dietary selenium on DNA adduct formation and on the activities of DNA adduct-repairing enzyme and oncogene expression in rat esophagus were investigated. The esophageal and forestomach tumors were induced by administration of NMBA by gavage with a total dose of 39 mg/kg body wt in rats and 12 mg/kg body wt in mice. Neither selenium dietary deficiency (Se < 0.02 ppm) nor selenium excess (2.0 ppm) showed any significant effect on the incidence of tumors or number of tumors per tumor-bearing animal. For the DNA adduct formation studies, rats were given a dose of NMBA intraperitoneally after six weeks on the different selenium-containing diets. No significant difference in the amount of the DNA adduct O6-methyldeoxyguanosine was found among the different selenium-treated groups. In a parallel group of rats that did not receive NMBA, the levels of esophageal O6-methyldeoxyguanosine DNA methyltransferase were not significantly altered by dietary selenium levels. The c-myc oncogene expression in rat esophagus was induced by the administration of NMBA (3 mg/kg body wt) by gavage once a week for eight weeks. Dietary selenium did not show any effects on its expression. On the basis of the results of these studies, dietary selenium has no effects in the NMBA-induced tumor model.
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PMID:Lack of effects of selenium on N-nitrosomethylbenzylamine-induced tumorigenesis, DNA methylation, and oncogene expression in rats and mice. 129 2

Preimplantation mouse embryos contain very high levels of DNA methyltransferase activity. We show here that the form of DNA methyltransferase (DNA MTase) in early embryos differs from the form found in other cells and tissues by a slightly higher mobility on gel electrophoresis. Levels of DNA MTase were found to be very high throughout preimplantation development even though levels of 5-methylcytosine (m5C) in nuclear DNA are known to undergo a substantial decline in the same period. Confocal laser scanning microscopy of mouse embryos stained with DNA MTase-specific antibodies showed striking developmentally regulated changes in the distribution of DNA MTase. From the oocyte stage to the four-cell-stage, most DNA MTase was concentrated in peripheral cytoplasm, and nuclei did not contain detectable DNA MTase. In four- and eight-cell embryos, DNA MTase was seen in cytoplasmic granules; and in eight-cell embryos, DNA MTase was also present in large amounts in nuclei. Nuclei of blastocysts stained only faintly, whereas the cytoplasmic granules remained prominent. Paradoxically, DNA MTase was found to be at its highest levels in nuclei at a developmental stage where levels of m5C in DNA are decreasing most rapidly. Changes in methylation patterns in preimplantation embryos are therefore proposed to be under the control of unidentified regulatory factors rather than DNA MTase itself; these regulatory factors could be members of the group that contains the products of the Ssm-1 and Imp-1 genes, which are involved in the regulation of genomic imprinting.
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PMID:Properties and localization of DNA methyltransferase in preimplantation mouse embryos: implications for genomic imprinting. 134 Apr 68

The CpG islands found at the 5' ends of many mammalian genes are typically unmethylated despite being both exposed to diffusible protein factors in nuclei and rich in CpG, the target site for DNA methyltransferase. We show here that the CpG islands associated with the human Thy-1 and profilin genes are inherently resistant to de novo methylation by purified murine DNA methyltransferase, and that the higher than expected tendency of CpG sites in islands to be flanked on both sides by G-C base pairs is the likely reason for the resistance. Several lines of evidence indicate that DNA methyltransferase does not make base-specific contacts with residues that flank CpG sites, and it is likely that CpG sites within islands are resistant to de novo methylation because of local conformational features such as ease of strand separation, minor groove dimensions, and alternative secondary structures. A role for minor groove contacts is consistent with the presence within a putative regulatory domain of numerous modified beta turn structural elements that can make minor groove contacts.
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PMID:CpG islands in mammalian gene promoters are inherently resistant to de novo methylation. 135 81

The gene coding for the ATCGAT specific BanIII DNA methyltransferase (M-BanIII) of Bacillus aneurinolyticus was cloned and its nucleotides sequenced. The coding region was assigned on the nucleotide sequence on the basis of the N-terminal amino acid sequence and molecular weight of the enzyme. The M-BanIII gene coded for a protein of 580 amino acid residues (MW 66,344). Comparison with other methylases indicated that the M-BanIII sequence contained a segment of tetra-amino acids, NPPY, characteristic of N6-adenine methylases. In addition, some homologous regions were found in the sequences of type II adenine methylases PaeR7I(CTCGAG), TaqI(TCGA) and PstI(CTGCAG), containing TCGA within the recognition sequences.
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PMID:Nucleotide sequence of the gene coding for the BanIII DNA methyltransferase in Bacillus aneurinolyticus. 136 40

O6-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein which plays an important role in chemotherapy, mutagenesis, and carcinogenesis. The specific activity of MGMT in female rat liver can be induced by approximately 20-fold by treatment of the rats with gamma-irradiation. Maximum response occurred 48 h after 15 Gy irradiation. MGMT levels in male rats were induced by only 3-fold. MGMT activity was also induced by irradiation of rat hepatoma H4IIE cells with a 3-fold increase noted after treatment with 3 Gy. Northern analysis and nuclear run-on assays indicated that the induction of MGMT was regulated at the transcriptional level. The radiation-mediated increase in MGMT was blocked by H7, a protein kinase inhibitor, but not by H89, an inhibitor of protein kinase A. Hydroxyl radicals may play a role in the induction mechanism since dimethyl sulfoxide, a radical scavenger, blocked the radiation-mediated increase in MGMT. MGMT activity was also increased by treatment of the cells with H2O2, in accordance with the involvement of activated oxygen species in the induction of MGMT. Finally, the addition of cycloheximide, an inhibitor of protein synthesis, prior to but not after irradiation, abolished the increase in MGMT activity.
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PMID:Irradiation-induced expression of O6-methylguanine-DNA methyltransferase in mammalian cells. 137 30

Although several hypomethylating agents such as 5-azadeoxycytidine and 5-fluorodeoxycytidine have been shown to activate transcription after incorporation into viral or cellular DNA, agents which selectively affect the methylation status of virus-infected cells have not been described. Studies on the antiviral effect of the methyldeoxycytidine (mdCyd) analogue trifluoromethyldeoxycytidine (F3mdCyd) showed significant antiviral activity against herpes simplex virus type 1 (HSV-1). This analogue of both dCyd and dThd is selectively incorporated into the DNA of herpesvirus infected cells due to the unique specificity of the herpesvirus thymidine kinase (TK) because the HSV-1 TK is both a dCyd and dThd kinase. In contrast, the deoxycytidine kinase of uninfected cells preferentially phosphorylates dCyd and has a poor affinity for F3mdCyd. F3mdCyd hemisubstituted M13 DNA displayed the same properties as mdCyd-substituted M13 DNA with respect to cleavage by restriction enzymes, and acted as an efficient template for eukaryotic DNA methyltransferase (S-adenosyl-L-methionine DNA (cytosine-5) methyltransferase: EC 2.1.1.37). Using the persistently infected CEM cell model system, the extent of DNA methylation was shown to increase in a dose-related manner when HSV-1-infected CEM cells were treated with increasing concentrations of F3mdCyd. Higher levels of methylation correlated with significant decreases in HSV-1 titers. Isoschizomer analyses followed by Southern blotting and hybridization with genomic HSV-1 DNA showed that DNA from HSV-1-infected, analogue-treated Vero cells was resistant to cleavage by restriction enzymes at a time when productive virus was not present in culture. We infer from these results that the methylation-like properties of the incorporated F3mdCyd occur concomitantly with, and appear to be involved in, the mechanisms of the analogue's antiviral effect towards HSV-1.
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PMID:Methylation of HSV-1 DNA as a mechanism of viral inhibition: studies of an analogue of methyldeoxycytidine: trifluoromethyldeoxycytidine (F3mdCyd). 138 26

We have examined the effects of the nitrosoureas, streptozotocin (STZ) and 1,3-bis(chloroethyl)-1-nitrosourea (BCNU), on a human multiple myeloma cell line, RPMI 8226, and its drug-resistant variants. Cell lines selected for doxorubicin (DOX) resistance alone displayed a STZ and BCNU cytotoxicity profile similar to that of the parent cell line. In contrast, two of the drug-resistant variants selected with DOX plus verapamil, an agent which inhibits P-glycoprotein-mediated multidrug resistance, displayed a collateral sensitivity to STZ and BCNU. Verapamil was included in the selection protocol because it has been shown to inhibit the P-glycoprotein-mediated multidrug resistance phenotype and is now in clinical trials as a chemosensitizing agent. The collateral sensitivity to these nitrosoureas seen in the DOX plus verapamil-selected cell lines is due to the functional loss of a DNA repair molecule, O6-Methylguanine DNA methyltransferase (MGMT). The functional loss of MGMT is secondary to the loss of MGMT gene expression. The loss of MGMT gene expression is not due to loss or gross rearrangement of the MGMT-coding region. If this selection pressure applied in vitro reflects the in vivo situation, then new chemotherapeutic strategies may be devised to exploit this phenomenon. These cell lines will serve as useful models for delineating mechanisms which govern MGMT expression.
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PMID:Collateral sensitivity to nitrosoureas in multidrug-resistant cells selected with verapamil. 138 86

The EcaI GGTNACC-specific DNA-adenine modification methyltransferase has been purified to apparent homogeneity. The active form of the DNA methyltransferase is a single polypeptide. The enzyme has a pH optimum at pH 8.0 and a temperature optimum at 25 degrees C. EcaI DNA methyltransferase transfers one methyl group to the adenine of the recognition site in a single binding event. The Km was 170 nM for DNA and 1.8 microM for the methyl donor S-adenosylmethionine. Methylated DNA is a competitive inhibitor with respect to DNA (Ki = 3.5 nM). The other product of the DNA-methylation reaction, S-adenosylhomocysteine was found to be a competitive inhibitor with respect to S-adenosylmethionine (Ki = 2.7 microM). The S-adenosylmethionine analog sinefungin was shown to be a very strong inhibitor (Ki = 3.5 nM) of the DNA methyltransferase reaction.
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PMID:Purification and biochemical characterization of the EcaI DNA methyltransferase. 139 13


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