DNA Polymerase Mechanisms in Viral Replication

Viral replication relies fundamentally on specialised DNA polymerases that orchestrate genome synthesis, fidelity control and interaction with viral and host factors. These enzymes exhibit remarkable diversity in structure and function, reflecting adaptations to distinct replication strategies among viruses. In double-stranded DNA viruses, protein-primed polymerases initiate synthesis by covalent attachment to a terminal primer protein, coupling strand displacement with high-fidelity elongation. In tailed bacteriophages and large eukaryotic viruses, family B polymerases combine 3′–5′ exonuclease proofreading with extensive processivity to ensure accurate genome reproduction. Retroviruses and hepadnaviruses employ reverse transcriptase activities to convert RNA templates into DNA, balancing error rate and adaptability. Key mechanistic features include conformational transitions between polymerisation and exonucleolytic domains, coordination of metal-ion-assisted catalysis, and the capacity to negotiate secondary structure or modified bases. Insights into viral polymerase function have illuminated antiviral targets, guided the design of polymerase-based diagnostics and inspired novel biotechnological tools. Understanding the interplay between enzyme architecture, accessory cofactors and replication origin recognition remains central to controlling viral propagation and harnessing polymerases for in vitro applications.

Research from Nature Portfolio

Recent studies have revealed the structural basis for coupling polymerisation and proofreading in the φ29 DNA polymerase. Site-directed mutagenesis of conserved residues in the exonuclease and finger domains demonstrated that Tyr101 and Thr189 contribute to processivity and fidelity by stabilising nascent duplex binding, while alterations of Gln180 enhance exonucleolytic turnover. Biochemical analyses combined with crystallographic modelling indicated water-mediated hydrogen-bond networks that govern the switch between synthesis and excision modes. These findings clarify how spatially distant active sites communicate to prevent replication errors and support the enzyme’s inherent strand displacement capacity, reinforcing φ29 polymerase as a paradigm for protein-primed DNA synthesis.

DNA Polymerase Mechanisms in Viral Replication publication trend

The graph below shows the total number of articles in dna polymerase mechanisms in viral replication across all publications each year (not limited to Nature Index journals).

Technical terms

DNA polymerase: Enzyme that catalyses the synthesis of DNA strands by adding nucleotides to a primer bound to a template.

3′–5′ exonuclease activity: Proofreading function that removes mismatched nucleotides from the 3′ end of a growing DNA strand.

Processivity: Measure of the number of nucleotides incorporated per binding event between polymerase and DNA.

Strand displacement: Ability of a polymerase to synthesise DNA while displacing the downstream strand without auxiliary helicases.

Protein-primed replication: Initiation mechanism in which a terminal protein provides a free hydroxyl group to prime DNA synthesis at genome termini.

References

1. Identification of a novel family B DNA polymerase from Enterococcus phage IME199 and its overproduction in Escherichia coli BL21(DE3). Microbial Cell Factories (2023).
2. New insights into the coordination between the polymerization and 3′-5′ exonuclease activities in ϕ29 DNA polymerase. Scientific Reports (2019).
3. Bacteriophage-Encoded DNA Polymerases—Beyond the Traditional View of Polymerase Activities. International Journal of Molecular Sciences (2022).