DNA synthesis machinery and nascent DNA

The DNA synthesis machinery and nascent DNA represent a critical therapeutic target complex primarily utilized in oncology and virology (Nature Reviews Molecular Cell Biology, 2017). This target encompasses the replisome—a multi-protein assembly including DNA polymerases, helicases, and primases—as well as the newly synthesized (nascent) DNA strands themselves (NIH, 2023). During the S-phase of the cell cycle, these components work in concert to ensure accurate genome duplication. Many chemotherapeutic agents, particularly nucleoside analogs like cytarabine and gemcitabine, target this process by mimicking natural deoxynucleotides (StatPearls, 2023). These drugs are incorporated into the nascent DNA strand, leading to DNA chain termination or the stalling of replication forks, which ultimately triggers apoptosis in rapidly dividing cells (Journal of Biological Chemistry, 2010). While highly effective against various malignancies, targeting this fundamental process often results in significant side effects due to the impact on healthy, rapidly proliferating tissues such as bone marrow and the intestinal epithelium (PubMed, 2021).

Other names

ReplisomeDNA replication machineryNascent DNA strandDNA replication complex

Inhibition of DNA polymerases and incorporation into nascent DNA strands leading to chain termination or replication fork arrest.