DNA polymerase III PolC-type (PolC)

Bacterial DNA polymerase III (Pol III) from Staphylococcus aureus is the essential enzyme complex responsible for the bulk of chromosomal DNA replication. In Gram-positive bacteria like S. aureus, the replicative machinery is distinct from Gram-negative models because it utilizes two different Pol III enzymes: PolC and DnaE. PolC is the primary replicative polymerase, performing the majority of leading and lagging strand synthesis and possessing intrinsic 3'-5' exonuclease activity for proofreading. DnaE in S. aureus is primarily involved in extending RNA primers before handing off the synthesis to PolC. Because PolC is essential for bacterial survival and lacks a direct human homolog, it serves as a high-priority target for the development of novel antibiotics, particularly against multi-drug resistant strains like MRSA. Drugs targeting this enzyme, such as 6-anilinouracils, typically act by competing with deoxyguanosine triphosphate (dGTP) or by forming a stable, inactive complex with the DNA template, effectively halting the replication fork and inducing bacterial cell death.

Other names

PolCDNA polymerase III alpha subunitReplicative DNA polymerasepolC gene productDPO3_STAA1

Inhibition of DNA synthesis by competing with dGTP or sequestering the enzyme into an inactive DNA-drug-protein complex, thereby stalling the replication fork and preventing chromosomal duplication.