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DNA polymerase III PolC-type subunit is a C-family replicative DNA polymerase that serves as the primary enzyme responsible for chromosomal DNA replication in Gram-positive bacteria, particularly those with low genomic GC content[2][10]. PolC catalyzes rapid DNA synthesis on both leading and lagging strands and possesses intrinsic 3' to 5' exonuclease activity for proofreading, contributing to high-fidelity replication[2][6]. The enzyme contains a unique N-terminal domain and structural features including a β-strand motif in its thumb domain that enables sensing of replication errors up to 8 nucleotides upstream of the active site, facilitating communication with the broader replisome machinery to trigger error correction[5]. PolC is universal among bacteria analyzed to date, making it essential for bacterial viability and representing a validated biological target for potential antimicrobial therapeutic development, though no clinically approved drugs currently target this enzyme[2]. Mutations in the polC gene have been shown to generate hypermutator bacterial phenotypes, suggesting the enzyme's critical role in maintaining genomic stability[8].
Inhibition of PolC would likely result in: - Inhibition of bacterial DNA replication - Disruption of both leading and lagging strand synthesis - Potential bacterial cell death or growth arrest
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