DNA polymerase III subunit alpha PolC (PolC)

DNA polymerase III subunit alpha PolC is the essential replicative enzyme responsible for chromosomal DNA synthesis in low G+C Gram-positive bacteria, including pathogens such as Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecalis (UniProt P13267). Unlike the DNA polymerase III (DnaE) found in Gram-negative bacteria like Escherichia coli, PolC possesses an intrinsic 3'-5' exonuclease proofreading activity and serves as the primary replicase for both leading and lagging strands in these organisms (Low et al., 2003; PMID: 12805257). Because PolC is structurally distinct from eukaryotic DNA polymerases, it represents a highly selective target for the development of narrow-spectrum antibiotics that do not interfere with human DNA replication (Daly et al., 2000; PMID: 10952585). Inhibitors of PolC, such as 6-anilinouracils, typically act by competing with dGTP for binding, thereby halting bacterial DNA replication and exerting a bactericidal effect (Wright & Brown, 1990). This target is particularly significant for addressing multi-drug resistant Gram-positive infections where traditional antibiotics may fail.

Other names

PolCDNA polymerase III alpha subunitReplicative DNA polymerase PolCDNA nucleotidyltransferaseDnaE1

Inhibition of DNA synthesis by competitive binding with deoxyguanosine triphosphate (dGTP) at the enzyme active site, which prevents the formation of the ternary complex and leads to termination of DNA chain elongation (Wright & Brown, 1990; PMID: 2190303).