DNA polymerase and DNA replication machinery (Replisome)

The DNA polymerase and DNA replication machinery, collectively known as the replisome, is a highly coordinated multi-protein assembly essential for the faithful duplication of genetic material prior to cell division (Nature Reviews Molecular Cell Biology: The replisome). This complex includes DNA polymerases (such as alpha, delta, and epsilon in eukaryotes), helicases, primases, and sliding clamps like PCNA, which work together to unwind the double helix and synthesize new DNA strands (Wikipedia: DNA polymerase). Because uncontrolled proliferation is a defining characteristic of cancer, components of the replication machinery are frequently targeted by chemotherapeutic agents, such as nucleoside analogs that disrupt DNA synthesis (NIH/NCBI: DNA replication as a target for anticancer drugs). Similarly, viral and bacterial DNA polymerases are primary targets for anti-infective drugs, which exploit structural differences between pathogen and host enzymes to achieve selectivity (PubChem: Cytarabine). Despite their therapeutic utility, drugs targeting the replication machinery often exhibit significant toxicity toward rapidly dividing healthy cells, particularly in the bone marrow and intestinal epithelium, leading to side effects like immunosuppression and mucositis.

Other names

DNA replication complexDNA-directed DNA polymerase complexReplication fork machineryDNA replication apparatus

Inhibition of DNA synthesis through competitive binding with natural deoxynucleoside triphosphates (dNTPs), leading to incorporation into the nascent DNA strand and subsequent chain termination or stalling of the replication fork (StatPearls: DNA Polymerase; NIH/NCBI: DNA replication as a target for anticancer drugs).