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The DNA/RNA synthesis and DNA methylation machinery refers to the collective group of enzymes and regulatory proteins responsible for the replication, transcription, and epigenetic modification of nucleic acids. This complex system includes DNA polymerases for replication, RNA polymerases for transcription, and DNA methyltransferases (DNMTs) for the addition of methyl groups to cytosine residues, which regulates gene expression [1][2]. Dysregulation of these processes is a hallmark of various pathologies, most notably cancer, where accelerated synthesis supports rapid proliferation and aberrant methylation leads to the silencing of tumor suppressor genes [3]. Therapeutic strategies targeting this machinery include antimetabolites that deplete nucleotide precursors, nucleoside analogs that incorporate into nascent strands to cause chain termination, and hypomethylating agents that restore normal gene expression patterns [4][5]. While these therapies are foundational in oncology and virology, their lack of absolute specificity for diseased cells often results in significant side effects, such as bone marrow suppression and mucosal damage [6].
Inhibition of nucleotide biosynthesis, competitive inhibition of DNA/RNA polymerases, induction of DNA chain termination, and covalent inhibition of DNA methyltransferases to induce hypomethylation [4][5][6].
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