Human DNA and RNA polymerases (DNAP/RNAP)

Human DNA and RNA polymerases represent a broad class of enzymes essential for the maintenance, replication, and expression of the human genome. DNA polymerases, including the replicative types alpha, delta, and epsilon, catalyze the template-directed polymerization of deoxyribonucleotides during DNA replication and repair (Source: Nature Reviews Molecular Cell Biology, 2016, PMID: 27357481). RNA polymerases, specifically Pol I, II, and III, are responsible for synthesizing various RNA species, with Pol II being the primary enzyme for messenger RNA transcription (Source: Cell, 2018, PMID: 29606353). These enzymes are critical therapeutic targets in oncology; for instance, nucleoside analogs like cytarabine and gemcitabine act as antimetabolites that inhibit DNA polymerase activity to induce apoptosis in rapidly dividing cancer cells (Source: Journal of Clinical Oncology, 2005, PMID: 15591251). However, the lack of high specificity for cancerous versus healthy cells often results in significant clinical toxicities, such as myelosuppression and gastrointestinal distress. Furthermore, off-target inhibition of mitochondrial DNA polymerase gamma by certain antiviral or antineoplastic agents can lead to severe mitochondrial dysfunction and organ toxicity (Source: Nucleic Acids Research, 2011, PMID: 21602186).

Other names

DNA-directed DNA polymeraseDNA-directed RNA polymeraseDNA nucleotidyltransferaseRNA nucleotidyltransferaseDNA polRNA pol

Inhibition of nucleic acid synthesis through competitive binding with natural nucleotides, induction of DNA chain termination, or direct binding to the enzyme complex to prevent translocation.