ArticleThe Journal of biological chemistry2012
JBP1 and JBP2 proteins are Fe2+/2-oxoglutarate-dependent dioxygenases regulating hydroxylation of thymidine residues in trypanosome DNA.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- Uncovering ParB-dependent and -independent subclasses of T-dioxygenases from bacteriophage.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Synthesis and Evaluation of the First Generation of Glycosylated Nucleoside Analogues as Potential Inhibitors of the Base J Metabolism in Kinetoplastid Parasites.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- 8-Oxoguanine: A Lesion, an Epigenetic Mark, or a Molecular Signal?International journal of molecular sciences · 2025Review
- Base-resolution profiling of 5-glyceryl-methylcytosine in Chlamydomonas reinhardtii via deaminase-assisted sequencing.Nucleic acids research · 2025Article
- Mono-allelic epigenetic regulation of polycistronic transcription initiation by RNA polymerase II inmBio · 2025Article
- Epigenetic marks or not? The discovery of novel DNA modifications in eukaryotes.The Journal of biological chemistry · 2024Review
- Knockout of protein phosphatase 1 in Leishmania major reveals its role during RNA polymerase II transcription termination.Nucleic acids research · 2023Article
- Behind Base J: The Roles of JBP1 and JBP2 on Trypanosomatids.Pathogens (Basel, Switzerland) · 2023Review
- Identification of a novel base J binding protein complex involved in RNA polymerase II transcription termination in trypanosomes.PLoS genetics · 2020Article
- The domain architecture of the protozoan protein J-DNA-binding protein 1 suggests synergy between base J DNA binding and thymidine hydroxylase activity.The Journal of biological chemistry · 2019Article
- Characterization and structure determination of a llama-derived nanobody targeting the J-base binding protein 1.Acta crystallographica. Section F, Structural biology communications · 2018Article
- Epigenetic Regulation of Transcription in Trypanosomatid Protozoa.Current genomics · 2018Review
- Genome-wide mapping of 5-hydroxymethyluracil in the eukaryote parasite Leishmania.Genome biology · 2017Article
- A method for the efficient and selective identification of 5-hydroxymethyluracil in genomic DNA.Biology methods & protocols · 2017Article
- Base J represses genes at the end of polycistronic gene clusters in Leishmania major by promoting RNAP II termination.Molecular microbiology · 2016Article
- Detection of uracil within DNA using a sensitive labeling method for in vitro and cellular applications.Nucleic acids research · 2016Article
- Histone H3 Variant Regulates RNA Polymerase II Transcription Termination and Dual Strand Transcription of siRNA Loci in Trypanosoma brucei.PLoS genetics · 2016Article
- Base J glucosyltransferase does not regulate the sequence specificity of J synthesis in trypanosomatid telomeric DNA.Molecular and biochemical parasitology · 2015Article
- Oxygen sensing by protozoans: how they catch their breath.Current opinion in microbiology · 2015Review
- Defining the sequence requirements for the positioning of base J in DNA using SMRT sequencing.Nucleic acids research · 2015Article
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8 authors at 2 institutions in 1 country.
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Abstract
We have recently demonstrated that O-linked glucosylation of thymine in trypanosome DNA (base J) regulates polymerase II transcription initiation. In vivo analysis has indicated that base J synthesis is initiated by the hydroxylation of thymidine by proteins (JBP1 and JBP2) homologous to the Fe(2+)/2-oxoglutarate (2-OG)-dependent dioxygenase superfamily where hydroxylation is driven by the oxidative decarboxylation of 2-OG, forming succinate and CO(2). However, no direct evidence for hydroxylase activity has been reported for the JBP proteins. We now demonstrate recombinant JBP1 hydroxylates thymine specifically in the context of dsDNA in a Fe(2+)-, 2-OG-, and O(2)-dependent manner. Under anaerobic conditions, the addition of Fe(2+) to JBP1/2-OG results in the formation of a broad absorption spectrum centered at 530 nm attributed to metal chelation of 2-OG bound to JBP, a spectroscopic signature of Fe(2+)/2-OG-dependent dioxygenases. The N-terminal thymidine hydroxylase domain of JBP1 is sufficient for full activity and mutation of residues involved in coordinating Fe(2+) inhibit iron binding and thymidine hydroxylation. Hydroxylation in vitro and J synthesis in vivo is inhibited by known inhibitors of Fe(2+)/2-OG-dependent dioxygenases. The data clearly demonstrate the JBP enzymes are dioxygenases acting directly on dsDNA, confirming the two-step J synthesis model. Growth of trypanosomes in hypoxic conditions decreases JBP1 and -2 activity, resulting in reduced levels of J and changes in parasite virulence previously characterized in the JBP KO. The influence of environment upon J biosynthesis via oxygen-sensitive regulation of JBP1/2 has exciting implications for the regulation of gene expression and parasite adaptation to different host niches.
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