Mycobacterial DnaQ is an Alternative Proofreader Ensuring DNA Replication Fidelity

Area of Science:

• Molecular Biology
• Genetics
• Microbiology

Background:

• DNA replication fidelity is crucial for preventing mutations.
• While Escherichia coli uses DnaQ (ε-exonuclease) for proofreading, mycobacteria primarily rely on the PHP domain of their replicative polymerase.
• An alternative DnaQ homolog exists in mycobacteria but its role in proofreading was unclear.

Conclusions:

• The alternative DnaQ protein functions as a proofreader in mycobacteria.
• Mycobacteria employ a dual-proofreading system involving both the PHP domain and DnaQ to ensure high replicative fidelity.
• The identified DnaQ variant highlights a mechanism for rapid adaptation and potential link to antimicrobial resistance in M. tuberculosis.