Cellular DNA polymerase complexes and replicating DNA (DNA Pol/DNA)

Cellular DNA polymerase complexes and replicating DNA constitute the essential molecular machinery for genomic duplication (Hübscher et al., 2002). This target includes the core replicative polymerases—alpha, delta, and epsilon—alongside the DNA template and associated proteins like the sliding clamp PCNA (Zeman & Cimprich, 2014). These complexes are critical for cell cycle progression, specifically during the S phase where they ensure high-fidelity copying of genetic material (Alberts et al., 2002). In clinical practice, this system is a major target for a wide array of anticancer agents, particularly antimetabolites and DNA-damaging drugs (StatPearls, 2023). Drugs like cytarabine and gemcitabine act as nucleoside analogs that are incorporated into DNA, leading to chain termination or polymerase stalling (PubChem). Other agents may directly inhibit the enzymatic activity of the polymerases or create physical barriers on the replicating DNA that cause replication fork collapse (Nature Reviews Cancer, 2011). Because these processes are most active in rapidly dividing cells, they provide a therapeutic window for treating malignancies (NIH). However, the lack of absolute specificity for cancer cells leads to characteristic toxicities in healthy, fast-dividing tissues like the hematopoietic system (Mayo Clinic). Modern research focuses on targeting specific components of the replication stress response to enhance the efficacy of these traditional polymerase-targeting drugs (Cell, 2017).

Other names

ReplisomeDNA replication machineryDNA polymerase alpha/delta/epsilon complexesReplicating DNA

Inhibition of DNA synthesis through competitive inhibition of DNA polymerases, incorporation into the growing DNA strand leading to chain termination, or induction of replication fork collapse (StatPearls, 2023; Nature Reviews Molecular Cell Biology, 2002).