Mechanism of action of nucleoside analogue inhibitors.
Deoxynucleoside analogues such as 5-aza-2-deoxycytidine (depicted by Z) are converted into the triphosphate inside S-phase cells and are incorporated in place of cytosine into DNA. Ribonucleosides such as 5-azacytidine or zebularine are reduced at the diphosphate level by ribonucleotide reductase for incorporation (not shown). Once in DNA, the fraudulent bases form covalent bonds with DNA methyltransferases (DNMTs), resulting in the depletion of active enzymes and the demethylation of DNA. Pink circles, methylated CpG; cream circles, unmethylated CpG.
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The behavior of a person's genes doesn't just depend on the genes' DNA sequence - it's also affected by so-called epigenetic factors. Changes in these factors can play a critical role in disease.
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