DNA and RNA polymerases and replicating DNA

DNA and RNA polymerases, along with the replicating DNA template, constitute the fundamental machinery for genetic replication and gene expression across all life forms (StatPearls, 2023). DNA polymerases are enzymes that synthesize new DNA strands by adding nucleotides to a primer, essential for cell division and DNA repair, while RNA polymerases catalyze the transcription of DNA into RNA (Nature Reviews Molecular Cell Biology, 2020). Replicating DNA is a vulnerable state of the genome where the double helix is unwound, making it a primary target for cytotoxic agents like alkylators and intercalators (NIH, 2024). In clinical practice, these targets are exploited to treat viral infections by using nucleoside analogs that act as chain terminators, such as acyclovir or sofosbuvir, which selectively inhibit viral polymerases (PubChem, 2024). In oncology, drugs like cytarabine or cisplatin target these processes to halt the rapid proliferation of malignant cells by inhibiting polymerase activity or inducing lethal DNA damage (PubMed, 2023). However, because these processes are also vital for healthy host cells, therapeutic intervention often results in significant side effects, including bone marrow suppression and organ toxicity (Journal of Clinical Oncology, 2022).

Other names

Nucleic acid polymerasesDNA replication machineryRNA transcription machineryDNA-dependent DNA polymeraseDNA-dependent RNA polymeraseReplication fork

Inhibition of nucleic acid synthesis through competitive inhibition of nucleotide binding, chain termination following incorporation into the nascent strand, or physical disruption of the DNA template to prevent polymerase progression.