Journal of Molecular Biology
Mechanism of action of eukaryotic DNA methyltransferase: Use of 5-azacytosine-containing DNA☆
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2020, Experimental HematologyCitation Excerpt :HMAs are chemical analogues of cytosine, which were originally developed as cytotoxic agents [41]. However, it was quickly established that when incorporated into DNA, they function as an inhibitor of all three DNMTs [42,43]. Azacitidine covalently traps DNMTs on DNA, resulting in genomewide DNA hypomethylation through passive dilution of methylated cytosine over multiple generations of cell division [44].
The anti-fecundity effect of 5-azacytidine (5-AzaC) on Schistosoma mansoni is linked to dis-regulated transcription, translation and stem cell activities
2018, International Journal for Parasitology: Drugs and Drug ResistanceEpigenetics: A primer for clinicians
2016, Blood ReviewsCitation Excerpt :Azanucleosides are incorporated into DNA in place of cytosine. As methylation is replicated, DNMTs become irreversibly bound to the aza-substituted ring, resulting in loss of enzyme function [192,193], passive demethylation of subsequently replicated DNA, [194–197] and gene re-expression. The unresolved reaction between the aza-substituted DNA base and the DNMT enzyme produces a bulky adduct which also results in DNA damage (described in Additional effects of these drugs below).
Inhibitors of DNA Methylation, Histone Deacetylation, and Histone Demethylation. A Perfect Combination for Cancer Therapy.
2016, Advances in Cancer ResearchCitation Excerpt :Azacytidine and decitabine were synthesized as cytostatic agents in 1964 (Sorm, Piskala, Cihak, & Vesely, 1964) and azacytidine was later found to be a natural product of Streptoverticillium ladakanus (Bergy & Herr, 1966; Hanka, Evans, Mason, & Dietz, 1966). Early clinical trials found both compounds to be too toxic for use, but in the 1980s, it was discovered that azacytidine could induce differentiation in cultured mouse embryo cells and inhibit the methylation of newly synthesized DNA (Jones & Taylor, 1980; Taylor & Jones, 1982). Studies were also emerging from the Baylin laboratory and others in the 1980s and 1990s regarding the existence of promoter CpG island hypermethylation and the correlation with transcriptional repression.
Computational fishing of new DNA methyltransferase inhibitors from natural products
2015, Journal of Molecular Graphics and ModellingCitation Excerpt :These are responsible of transferring a methyl group from S-adenosyl-l-methionine (SAM) to the carbon-5 position of cytosine in DNA. This mechanism has been proposed for several authors (Fig. 1) [6–9]. Currently, three types of cytosine-5 DNMTs have been identified, including two de novo DNA methyltransferases; DNMT3A and DNMT3B, which establish the methylation patterns during embryonic development in mammals and in differentiated cells [10,11]; and DNMT1, the most abundant and active of these enzymes responsible for copying the methylation pattern of DNA during cell division [12,13].
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This work was supported by grant no. GM30892 from the National Institutes of Health.