ArticleNature genetics2015
DNA replication fidelity in Mycobacterium tuberculosis is mediated by an ancestral prokaryotic proofreader.
Article in Nature genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 77 citations in OpenAlex.
- Diversity and distribution of bacterial DNA polymerases.Nucleic acids research · 2026Article
- Hypermutability ofEmerging microbes & infections · 2025Article
- Identification of determinants of high-fidelity DNA synthesis in Mycobacterium smegmatis DnaE1 through in silico and in vivo approaches.Nucleic acids research · 2025Article
- Characterization of DnaB-DnaG Interaction in M. tuberculosis Using Small-Angle X-ray Scattering-Based Dissociation Assay.Chembiochem : a European journal of chemical biology · 2025Article
- Genome wide analyses reveal the role of mutator phenotypes in Mycobacterium tuberculosis drug resistance emergence.npj antimicrobials and resistance · 2025Article
- An additional proofreader contributes to DNA replication fidelity in mycobacteria.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- A nucleoid-associated protein is involved in the emergence of antibiotic resistance by promoting the frequent exchange of the replicative DNA polymerase inbioRxiv : the preprint server for biology · 2024Article
- Engineering of the DNA replication and repair machinery to develop binary mutators for rapid genome evolution of Corynebacterium glutamicum.Nucleic acids research · 2023Article
- RecA-NT homology motif in ImuB is essential for mycobacterial ImuA'-ImuB protein interaction and mutasome function.bioRxiv : the preprint server for biology · 2023Article
- High-Throughput Exonuclease Assay Based on the Fluorescent Base Analogue 2-Aminopurine.ACS omega · 2023Article
- Distinctive roles of translesion polymerases DinB1 and DnaE2 in diversification of the mycobacterial genome through substitution and frameshift mutagenesis.Nature communications · 2022Article
- Noncanonical prokaryotic X family DNA polymerases lack polymerase activity and act as exonucleases.Nucleic acids research · 2022Article
- The essentialScience advances · 2022Article
- DNA-Dependent Binding of Nargenicin to DnaE1 Inhibits Replication inACS infectious diseases · 2022Article
- The within-host evolution of antimicrobial resistance in Mycobacterium tuberculosis.FEMS microbiology reviews · 2021Review
- Review
- Compromised base excision repair pathway in Mycobacterium tuberculosis imparts superior adaptability in the host.PLoS pathogens · 2021Article
- Nonredundant functions of Mycobacterium tuberculosis chaperones promote survival under stress.Molecular microbiology · 2021Article
- Novel Antibiotics Targeting Bacterial Replicative DNA Polymerases.Antibiotics (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
The DNA replication machinery is an important target for antibiotic development in increasingly drug-resistant bacteria, including Mycobacterium tuberculosis. Although blocking DNA replication leads to cell death, disrupting the processes used to ensure replication fidelity can accelerate mutation and the evolution of drug resistance. In Escherichia coli, the proofreading subunit of the replisome, the ɛ exonuclease, is essential for high-fidelity DNA replication; however, we find that the corresponding subunit is completely dispensable in M. tuberculosis. Rather, the mycobacterial replicative polymerase DnaE1 itself encodes an editing function that proofreads DNA replication, mediated by an intrinsic 3'-5' exonuclease activity within its PHP domain. Inactivation of the DnaE1 PHP domain increases the mutation rate by more than 3,000-fold. Moreover, phylogenetic analysis of DNA replication proofreading in the bacterial kingdom suggests that E. coli is a phylogenetic outlier and that PHP domain-mediated proofreading is widely conserved and indeed may be the ancestral prokaryotic proofreader.
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