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DNA and its associated replication machinery, collectively known as the replisome, constitute a fundamental target in oncology and infectious disease (StatPearls, DNA Replication). This complex includes essential enzymes such as DNA polymerases, helicases, primases, and topoisomerases that work in concert to ensure accurate genome duplication during the S-phase of the cell cycle (Nature Education, Replisome). In cancer, these processes are often dysregulated to support rapid cellular proliferation, making them susceptible to cytotoxic agents that induce DNA damage or inhibit synthesis (NIH, Cancer Treatment). Similarly, many antimicrobial and antiviral therapies specifically target bacterial or viral versions of these enzymes, such as DNA gyrase or viral DNA polymerase, to halt pathogen replication (PubMed, Mechanism of Action of Quinolones). While highly effective, targeting DNA replication often leads to significant side effects due to the impact on other rapidly dividing healthy cells, such as those in the bone marrow and gastrointestinal tract (PubChem, Cisplatin). These therapies remain a cornerstone of clinical practice despite the development of more specific targeted agents.
Inhibition of DNA synthesis through DNA cross-linking, intercalation, inhibition of DNA polymerases, or inhibition of topoisomerases.
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