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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The symmetry of the responses of the human DNA (cytosine-5)methyltransferase to alternative placements of 5-methylcytosine in model oligodeoxynucleotide duplexes containing unusual structures has been examined. The results of these experiments more clearly define the DNA recognition specificity of the enzyme. A simple three-nucleotide recognition motif within the CG dinucleotide pair can be identified in each enzymatically methylated duplex. The data can be summarized by numbering the four nucleotides in the dinucleotide pair thus: 1 4/2 3. With reference to this numbering scheme, position 1 can be occupied by cytosine or 5-methylcytosine; position 2 can be occupied by guanosine or inosine; position 3, the site of enzymatic methylation, can be occupied only by cytosine; and position 4 can be occupied by guanosine, inosine, O6-methylguanosine, cytosine, adenosine, an abasic site, or the 3' hydroxyl group at the end of a gapped molecule. Replacing the guanosine normally found at position 4 with any of the moieties introduces unusual (non-Watson-Crick) pairing at position 3 and generally enhances methylation of the cytosine at that site. The exceptional facility of the enzyme in actively methylating unusual DNA structures suggests that the evolution of the DNA methyltransferase, and perhaps DNA methylation itself, may be linked to the biological occurrence of unusual DNA structures.
J Mol Biol 1991 Jan 05
PMID:Recognition of unusual DNA structures by human DNA (cytosine-5)methyltransferase. 198 79

A region upstream of the mouse adenine phosphoribosyltransferase (aprt) gene has a well characterized methylation pattern for HpaII/MspI sites. When an unmethylated plasmid construct containing this region was transfected into P19 mouse teratocarcinoma stem cells appropriate de novo methylation was observed. However, de novo methylation was significantly reduced when this plasmid was introduced into a differentiated derivative of the P19 stem cell line. Finally, a position effect for de novo methylation was shown by demonstrating methylation of a normally unmethylated HpaII/MspI site when it was placed in this upstream region. This system should prove useful for elucidating DNA signals for de novo methylation and changes in DNA methyltransferase activities that occur during cellular differentiation.
Somat Cell Mol Genet 1991 Mar
PMID:Region- and cell type-specific de novo DNA methylation in cultured mammalian cells. 201 93

The gene encoding the Neisseria lactamica III DNA methyltransferase (M.NlaIII) which recognizes the sequence CATG has been cloned and expressed in Escherichia coli. DNA sequencing of a 3.125 kb EcoRI-PstI fragment localizes the M. NlaIII gene to a 334 codon open reading frame (ORF) and identifies, 468 bp downstream, a second ORF of 313 amino acids, which is referred to as M.NlaX. Both proteins are detectable in the E. coli coupled in vitro transcription-translation system; they are apparently expressed from separate N. lactamica promoters. The N-terminal half of the previously characterized M.FokI, which methylates adenine in one of the DNA strands with its asymmetric recognition sequence (GGATG), is found to have 41% sequence identity and a further 11.7% sequence similarity with M.NlaIII. Among the conserved amino acids is the wellknown DPPY sequence motif. With one exception, analysis of the nucleotides coding for the DP dipeptide in all known DPPY sequences shows the presence of an inherent DNA adenine methylation (dam) recognition site of GATC. A low level of expression of M.NlaX in E. coli prevents the elucidation of its sequence recognition specificity. Sequence analysis of M.NlaX shows that it is closely related to the group of monospecific 5-methylcytosine DNA methyltransferases (M.EcoRII, Dcm, M.HpaII and M.HhaI) which all have a modified cytosine at the second position of the recognition sequences. Both M.EcoRII and Dcm amino acid sequences are about 50% identical with M.NlaX; a considerable degree of sequence identity is found in the so-called variable region which is believed to be responsible for sequence recognition specificity. M.NlaX is probably the counterpart to the E. coli Dcm in N. lactamica.
Mol Gen Genet 1990 Oct
PMID:Cloning and characterization of two tandemly arranged DNA methyltransferase genes of Neisseria lactamica: an adenine-specific M.NlaIII and a cytosine-type methylase. 227 28

The cell cycle-dependent and proliferation-associated expression of the enzyme DNA methyltransferase has been evaluated immunocytochemically in synchronized L-132 human embryonic lung cells, using the anti-DNA methyltransferase monoclonal antibody M1F6D7/5C10. DNA methyltransferase-reactivity was firstly seen in mid-G1 cells. An intense and granular reaction in the cell nuclei with a sparing of the nucleoli was observed in addition to a homogenous and faint cytoplasmic staining. The staining intensity in the cell nuclei increased progressively up to mitosis. In early mitotic cells an intense perichromosomal staining was observed in addition to a homogenous staining of cyto- and karyoplasm after the resolving of the core membrane. In late mitosis the staining intensity decreased rapidly. Early G1 cells and density inhibited, resting G0 cells showed no DNA methyltransferase reactivity at all. Our results indicate that anti-DNA methyltransferase monoclonal antibodies could become valuable tools to detect proliferating cells in cell cultures and tissues.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:Proliferation-associated expression of DNA methyltransferase in human embryonic lung cells. 256 84

Infection of rat embryo cells with herpes simplex virus type 2 caused undermethylation of host cell DNA synthesized during infection. DNA made prior to infection was not demethylated, but some of its degradation products, including methyl dCMP, were incorporated into viral DNA. The use of mutant virus showed that some viral DNA synthesis appears to be required for the inhibition of methylation. Inhibition of methylation cannot be explained by an absence of DNA methyltransferase as the activity of this enzyme did not change during the early period of infection. Inhibition of host cell DNA methylation may be an important step in the transformation of cells by herpesviruses, and various transformed cell lines tested showed reduced levels of DNA methylation.
Mol Cell Biol 1988 Apr
PMID:Hypomethylation of host cell DNA synthesized after infection or transformation of cells by herpes simplex virus. 283 42

Analysis of the enzymatic methylation of oligodeoxynucleotides containing multiple C-G groups showed that hemimethylated sites in duplex oligomers are not significantly methylated by human or murine DNA methyltransferase unless those sites are capable of being methylated de novo in the single- or double-stranded oligomers. Thus, the primary sequence of the target strand, rather than the methylation pattern of the complementary strand, determines maintenance methylation. This suggests that de novo and maintenance methylation are the same process catalyzed by the same enzyme. In addition, the study revealed that complementary strands of oligodeoxynucleotides are methylated at different rates and in different patterns. Both primary DNA sequence and the spacing between C-G groups seem important since in one case studied, maximal methylation required a specific spacing of 13 to 17 nucleotides between C-G pairs.
Mol Cell Biol 1986 Apr
PMID:Primary DNA sequence determines sites of maintenance and de novo methylation by mammalian DNA methyltransferases. 302 72

Alkylation at the O6 position of guanine leading to miscoding during DNA replication has been shown to correlate with mutagenesis both in bacteria and mammalian cells. The widely used Chinese hamster ovary cells (CHO) are unable to remove O6-methylguanine (O6-meG) due to the absence of O6-meG DNA methyltransferase (MT) activity. Recently Ding et al. [Mol. Cell. Biol. (1985) 5, 3293-3296] transfected CHO cells with human liver DNA obtaining a line provided with a function for the repair of O6-meG. We confirmed the presence of MT activity in this particular clone (14,300 molecules/cell). We used this MT-proficient cell line as compared with the original MT-deficient CHO cell line to analyse the relevance of repair of this lesion on cell killing, ouabain resistance (ouar) mutations and sister chromatid exchanges (SCEs) induced by methylating agents. MT-proficient cells were more resistant than MT-deficient ones to the cytotoxic and mutagenic effects of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and N-methyl-N-nitrosourea (MNU). Furthermore a lower number of MNNG-induced SCEs were found in MT-proficient CHO than in MT-deficient cells. Similar ouar mutation frequencies were recorded in the two cell lines after 4-nitroquinoline-1-oxide (4NQO) treatment showing that the differences in cytotoxicity and mutagenesis are restricted to treatment with alkylating agents.
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PMID:Cytotoxicity, mutations and SCEs induced by methylating agents are reduced in CHO cells expressing an active mammalian O6-methylguanine-DNA methyltransferase gene. 311 13

The Escherichia coli ada-alkB operon encodes a 39-kDa protein (Ada) that is a DNA-repair methyltransferase and a 27-kDa protein (AlkB) of unknown function. By DNA blot hybridization analysis we show that the alkylation-sensitive E. coli mutant BS23 [Sedgwick, B. & Lindahl, T. (1982) J. Mol. Biol. 154, 169-175] is a deletion mutant lacking the entire ada-alkB operon. Despite the absence of the ada gene and its product, the cells contain detectable levels of a DNA-repair methyltransferase activity. We conclude that the methyltransferase in BS23 cells is the product of a gene other than ada. A similar activity was detected in extracts of an ada-10::Tn10 insertion mutant of E. coli AB1157. This DNA methyltransferase has a molecular mass of about 19 kDa and transfers the methyl groups from O6-methylguanine and O4-methylthymine in DNA, but not those from methyl phosphotriester lesions. This enzyme was not induced by low doses of alkylating agent and is expressed at low levels in ada+ and a number of ada- E. coli strains.
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PMID:A second DNA methyltransferase repair enzyme in Escherichia coli. 328 37

A naturally occurring methylation inhibitor isolated from rabbit liver and named methinin inhibits a number of methyltransferases. Methinin is a low-molecular-weight compound (1,400) that has an active amine group. This compound inhibits the DNA methyltransferase of human erythroleukemia cells (K562) in vitro. When the K562 cells were grown in medium containing methinin, fetal hemoglobin was produced. Small but detectable amounts of adult hemoglobin were also produced. Methinin was not toxic to these cells. The overall rate of genomic DNA methylation was reduced by 60% in cells grown in medium containing methinin. Southern blots of genomic DNA from methinin-treated cells and untreated cells hybridized to a 32P-labeled globin gene probe showed that one site in the globin gene region was hypomethylated. Methinin is a naturally occurring compound which inhibits DNA methylation both in vitro and in vivo.
Mol Cell Biol 1987 May
PMID:Naturally occurring methylation inhibitor: DNA hypomethylation and hemoglobin synthesis in human K562 cells. 347 16

A DNA methyltransferase was isolated from a eucaryotic, Chlorella-like green alga infected with the virus PBCV-1. The enzyme recognized the sequence GATC and methylated deoxyadenosine solely in GATC sequences. Host DNA, which contains GATC sequences, but not PBCV-1 DNA, which contains GmATC sequences, was a good substrate for the enzyme in vitro. The DNA methyltransferase activity was first detected about 1 h after viral infection; PBCV-1 DNA synthesis and host DNA degradation also began at about this time. The appearance of the DNA methyltransferase activity required de novo protein synthesis, and the enzyme was probably virus encoded. Methylation of DNAs with the PBCV-1-induced methyltransferase conferred resistance of the DNAs to a PBCV-1-induced restriction endonuclease enzyme described previously (Y. Xia, D. E. Burbank, L. Uher, D. Rabussay, and J. L. Van Etten, Mol. Cell. Biol. 6:1430-1439). We propose that the PBCV-1-induced methyltransferase protects viral DNA from the PBCV-1-induced restriction endonuclease and is part of a virus-induced restriction and modification system in PBCV-1-infected Chlorella cells.
Mol Cell Biol 1986 May
PMID:DNA methyltransferase induced by PBCV-1 virus infection of a Chlorella-like green alga. 353 3


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