General cellular DNA synthesis machinery

The general cellular DNA synthesis machinery, often referred to as the replisome, is a complex multi-protein system responsible for the accurate and efficient duplication of the genome during the S phase of the cell cycle [StatPearls, 2023]. Key components of this machinery include DNA polymerases (alpha, delta, and epsilon), helicases, primases, and topoisomerases, which work in a coordinated fashion to unwind the double helix and synthesize new DNA strands [Nature Reviews Cancer, 2013]. Because rapid cell division is a hallmark of both cancer and various infectious pathogens, this machinery serves as a primary target for a wide array of therapeutic agents [NCBI, 2022]. Antimetabolites interfere with the production of nucleotide precursors, while direct inhibitors of DNA polymerase or topoisomerases disrupt the physical process of replication and can induce lethal DNA damage [StatPearls, 2023]. However, because these processes are fundamental to all dividing cells, drugs targeting this machinery often exhibit significant side effects, such as bone marrow suppression and gastrointestinal distress, due to their impact on healthy, rapidly proliferating tissues [NCBI, 2022].

Other names

DNA replication machineryReplisomeDNA synthesis pathwayDNA replication complex

Inhibition of nucleotide precursor synthesis (antimetabolites), direct inhibition of DNA polymerase enzymes, induction of DNA strand breaks via topoisomerase inhibition, and premature chain termination during DNA elongation [StatPearls, 2023; NCBI, 2022].