ArticlePLoS pathogens2013
Mycobacterial MazG safeguards genetic stability via housecleaning of 5-OH-dCTP.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- A Comprehensive Understanding ofCurrent issues in molecular biology · 2026Review
- Molecular basis of DosR-dependent transcription activation in Mycobacterium tuberculosis.Nature communications · 2026Article
- Genomic Surveillance of 3R Genes Associated with Antibiotic Resistance inAntibiotics (Basel, Switzerland) · 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
- Structural analysis of the housecleaning nucleoside triphosphate pyrophosphohydrolase MazG fromFrontiers in microbiology · 2023Article
- HEmerging microbes & infections · 2022Article
- Article
- Phenotypic adaptation ofFrontiers in cellular and infection microbiology · 2022Review
- Changes in the genomes and methylomes of threeFrontiers in microbiology · 2022Article
- Interception of host fatty acid metabolism by mycobacteria under hypoxia to suppress anti-TB immunity.Cell discovery · 2021Article
- Housecleaning of pyrimidine nucleotide pool coordinates metabolic adaptation of nongrowing Mycobacterium tuberculosis.Emerging microbes & infections · 2019Article
- Nano-metal oxides induce antimicrobial resistance via radical-mediated mutagenesis.Environment international · 2018Article
- Incomplete base excision repair contributes to cell death from antibiotics and other stresses.DNA repair · 2018Review
- Genome Sequences of Ilzat and Eleri, Two Phages Isolated Using Microbacterium foliorum NRRL B-24224.Genome announcements · 2018Article
- Lysine acetylation of DosR regulates the hypoxia response of Mycobacterium tuberculosis.Emerging microbes & infections · 2018Article
- Oxidation of dCTP contributes to antibiotic lethality in stationary-phase mycobacteria.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Antibiotic killing through oxidized nucleotides.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- SMRT genome assembly corrects reference errors, resolving the genetic basis of virulence in Mycobacterium tuberculosis.BMC genomics · 2017Article
- DCTPP1 attenuates the sensitivity of human gastric cancer cells to 5-fluorouracil by up-regulating MDR1 expression epigenetically.Oncotarget · 2016Article
- The Impact of Non-Enzymatic Reactions and Enzyme Promiscuity on Cellular Metabolism during (Oxidative) Stress Conditions.Biomolecules · 2015Review
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Generation of reactive oxygen species and reactive nitrogen species in phagocytes is an important innate immune response mechanism to eliminate microbial pathogens. It is known that deoxynucleotides (dNTPs), the precursor nucleotides to DNA synthesis, are one group of the significant targets for these oxidants and incorporation of oxidized dNTPs into genomic DNA may cause mutations and even cell death. Here we show that the mycobacterial dNTP pyrophosphohydrolase MazG safeguards the bacilli genome by degrading 5-OH-dCTP, thereby, preventing it from incorporation into DNA. Deletion of the (d)NTP pyrophosphohydrolase-encoding mazG in mycobacteria leads to a mutator phenotype both under oxidative stress and in the stationary phase of growth, resulting in increased CG to TA mutations. Biochemical analyses demonstrate that mycobacterial MazG can efficiently hydrolyze 5-OH-dCTP, an oxidized nucleotide that induces CG to TA mutation upon incorporation by polymerase. Moreover, chemical genetic analyses show that direct incorporation of 5-OH-dCTP into mazG-null mutant strain of Mycobacterium smegmatis (Msm) leads to a dose-dependent mutagenesis phenotype, indicating that 5-OH-dCTP is a natural substrate of mycobacterial MazG. Furthermore, deletion of mazG in Mycobacterium tuberculosis (Mtb) leads to reduced survival in activated macrophages and in the spleen of infected mice. This study not only characterizes the mycobacterial MazG as a novel pyrimidine-specific housecleaning enzyme that prevents CG to TA mutation by degrading 5-OH-dCTP but also reveals a genome-safeguarding mechanism for survival of Mtb in vivo.
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