Cellular DNA and DNA synthesis machinery (Replisome) (DNA/Replisome)

Cellular DNA and the DNA synthesis machinery constitute a broad class of therapeutic targets essential for cell division and genetic stability. This target complex includes the physical DNA template and the enzymatic assembly known as the replisome, which comprises DNA polymerases, helicases, primases, and topoisomerases [1, 4]. In proliferating cells, particularly malignant ones, these components are hyperactive to support rapid expansion, making them primary targets for traditional chemotherapy [2]. Drugs interacting with this machinery function through various mechanisms, such as forming DNA adducts, inhibiting the synthesis of nucleotide precursors, or blocking the strand-elongation activity of polymerases [2, 3]. Because these processes are also vital for healthy regenerating tissues, such as the hematopoietic system and gastrointestinal lining, drugs targeting this machinery often exhibit a narrow therapeutic index and significant systemic toxicity [1, 5]. Modern applications often involve combining these broad-spectrum agents with targeted therapies to enhance efficacy while managing the substantial safety concerns associated with DNA damage and replication stress [4, 6].

Other names

DNA replication machineryReplisomeGenomic DNADNA synthesis apparatusDNA replication complex

Inhibition of DNA synthesis through nucleotide depletion, direct DNA damage via alkylation or intercalation, and inhibition of replication enzymes such as DNA polymerases and topoisomerases [1, 2, 4].