Methylation of DNA bases

Wiaderkiewicz R, Walter Z, Reimschussel W. 1986. Sites of methylation of DNA bases by the action of organophosphoms insecticides in vitro. Acta Biochim Pol 33 73-85. 

D. F. V. Lewis and V. S. Griffiths, Xenobiotica, 17, 769 (1987). Molecular Electrostatic Potential Energies and Methylation of DNA Bases A Molecular Orbital-Generated Quantitative Structure-Activity Relationship. 

Footprinting dimethyl sulfate. Methylation of DNA bases occurs at regions not protected... 

Swenberg JA, Cooper HK, Bucheler J, et al. 1979. 1,2-Dimethylhydrazine-induced methylation of DNA bases in various rat organs and the effect of pretreatment with disulfiram. Cancer Res 39 465-467. 

The tumor-promoting activity of OA can be also partially related to other actions at cellular level, such as oxidation of different substrates, methylation of DNA bases, and inhibitory mechanisms of gap intracellular communication, which is believed to be of importance in the promotion stage of carcinogenesis. An additional factor hypothesized to contribute to the tumor promotion by OA is amplification of genes conferring multidrug resistance to cells. ... 

Connell, J.R. and Medcalf, A.S. (1982). The induction of SCE and chromosomal aberrations with relation to specific base methylation of DNA in Chinese hamster cells by N-methyl-n-nitrosourea and dimethyl sulphate. Carcinogenesis 3 385-390. 

Methylation of certain bases within DNA molecules plays a major role in gene expression, as is evidenced by the transcriptional silencing of X chromosome genes through methylation. The following are recent reviews on the molecular and physical properties of these enzymes [EC 2.1.1.x]. See also specific methyltransferase... 

In the experiment described in Section 3.1.3, in which Syrian hamsters were given hydrazine sulfate in the drinking-w ater for two years, the levels of methylation of DNA guanine in liver, kidney and lung were measured. Both NI- and Gs-methylguanme were readily detectable at six months of exposure, but only trace amounts of these bases were detected after 12 months of exposure these bases were again detected in liver DNA at exposure times of 18 and 24 months (Bosan et al., 1987). 

A stretch of DNA containing the mismatched base is excised from the unmethylated strand, repair synthesis to replace excised DNA and full methylation of DNA... 

A DNA modification which changes gene transcription is methylation of nucleotide bases. Heterochromatin contains heavily methylated DNA which cannot be transcribed. Genes in euchromatin are less methylated and are transcribable. Methylation at C5 of cytosine in CpG sequences by a methyltransferase, with 5-adenosyl methionine (SAM) as methyl donor, silences genes in heterochromatin. Methylation may affect the higher-order structure of DNA and may impede access of the transcriptional machinery to DNA. Members of the histone Hj family have been associated with transcriptional repression, because these histones bind preferentially to methylated CpG sequences (Fig. 9.10).4i... 

Among the acceptors modified by 5 -adenosylmethionine are specific bases in DNA. The methylation of DNA protects bacterial DNA from cleavage by restriction enzymes (Section 9.3). The base to be methylated is flipped out of the DNA double helix into the active site where it can accept a methyl group from 5 -adenosylmethionine (Figure 24.15). A recurring 5 -adenosylmethionine-binding domain is present in many SAM-dependent methylases. 

Change in DNA minor base composition can be observed as a decreased level of methylation of the base 5-methyl deoxycytidine. 

Azacytidine, after conversion to a phosphorylated derivative, arrests the DNA synthesis phase of the cell cycle. It also affects methylation of certain bases, which leads to hypomethylation (Chapter 26). 

In the methylation of DNA, specific methylases catalyse transfer of methyl groups from SAM to the 6-amino groups of adenine residues and C5 of cytosine. A specific pattern of methylation serves to protect DNA from the cell s own Restriction endonucleases (see) these enzymes destroy the DNA of invading viruses. The DNA of viruses that are able to replicate within a particular host are protected from the endonucleases by methylation of bases at the endonuclease-sensitive sites. 

For methyl-methan-sulphonate besides confirming its already known actions (that is methylation of the bases, formation of labile apur-inic sites and therefore intrastrand breakage (see data of thermal stability and viscosity) that are at the basis of its genotoxicity (18), we can add that in our experimental conditions the breakage formation is more evident in direct treatment of DNA than adding the compound to cell cultures. 

Host-Induced Restriction and Modification A genetic system found in bacteria whereby a genetic element (often a plasmid) encodes both an enzyme for the methylation of DNA at a specific base sequence and an Endonuclease that cleaves umnethylated DNA at that sequence. The system thus restricts the DNA that can survive in the cell to DNA that is modified by methylation at the correct sequences. 

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