Evidence map›Paper›PMID 24891501›Full record

ArticleThe Journal of biological chemistry2014

Identification of the glucosyltransferase that converts hydroxymethyluracil to base J in the trypanosomatid genome.

Whitney Bullard, Jessica Lopes da Rosa-Spiegler, Shuo Liu, Yinsheng Wang, Robert Sabatini

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
4.5field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 63 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Detection of Genomic Uracil Patterns.International journal of molecular sciences · 2021
    Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Nucleocytoplasmic O-glycosylation in protists.Current opinion in structural biology · 2019
    Review
  16. Identification ofMolecules (Basel, Switzerland) · 2019
    Article
  17. Article
  18. CRISPR/Cas9 and glycomics tools forThe Journal of biological chemistry · 2019
    Article
  19. Characterization and structure determination of a llama-derived nanobody targeting the J-base binding protein 1.Acta crystallographica. Section F, Structural biology communications · 2018
    Article
  20. Sequencing 5-Hydroxymethyluracil at Single-Base Resolution.Angewandte Chemie (International ed. in English) · 2018
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Whitney BullardFrom the Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602 and.
Jessica Lopes da Rosa-SpieglerFrom the Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602 and.
Shuo Liuthe Environmental Toxicology Graduate Program and.
Yinsheng Wangthe Environmental Toxicology Graduate Program and Department of Chemistry, University of California, Riverside, California 92521.
Robert SabatiniFrom the Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602 and rsabatini@bmb.uga.edu.
University of Georgia · USUniversity of California, Riverside · US

Funding

TR&D1: Stem Cell and Induced Pluripotent Stem Cell Resources (Pages 116-134)P41GM103490 · NIGMS · UNIVERSITY OF GEORGIA · PI PIERCE, J. MICHAEL · 2012 to 2018
$13.7M
Recombinant Production of Glycosylation Enzymes for Biochem/Structural StudiesP01GM107012 · NIGMS · UNIVERSITY OF GEORGIA · PI PRESTEGARD, JAMES H. · 2013 to 2017
$7.5M
Training in Tropical and Emerging Global Diseases - SupplementT32AI060546 · NIAID · UNIVERSITY OF GEORGIA (UGA) · PI Silvia N Moreno, Vasant Muralidharan · 2004 to 2026
$5.1M
Oxidative DNA Damage and CpG MutagenesisR01CA101864 · NCI · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI WANG, YINSHENG · 2004 to 2015
$2.8M
Biosynthesis and function of base J in T. bruceiR56AI063523 · NIAID · UNIVERSITY OF GEORGIA · PI SABATINI, ROBERT S · 2011 to 2011
$384k
NCI NIH HHS R01 CA101864NIAID NIH HHS 2R56AI063523-07A1NIAID NIH HHS R56 AI063523NIAID NIH HHS T32 AI060546NIGMS NIH HHS P01 GM107012NIGMS NIH HHS P01GM107012NIGMS NIH HHS P41 GM103490NIGMS NIH HHS P4GM103490
6 · The paper itself

Abstract

O-linked glucosylation of thymine in DNA (base J) is an important regulatory epigenetic mark in trypanosomatids. β-d-glucopyranosyloxymethyluracil (base J) synthesis is initiated by the JBP1/2 enzymes that hydroxylate thymine, forming 5-hydroxymethyluracil (hmU). hmU is then glucosylated by a previously unknown glucosyltransferase. A recent computational screen identified a possible candidate for the base J-associated glucosyltransferase (JGT) in trypanosomatid genomes. We demonstrate that recombinant JGT utilizes uridine diphosphoglucose to transfer glucose to hmU in the context of dsDNA. Mutation of conserved residues typically involved in glucosyltransferase catalysis impairs DNA glucosylation in vitro. The deletion of both alleles of JGT from the genome of Trypanosoma brucei generates a cell line that completely lacks base J. Reintroduction of JGT in the JGT KO restores J synthesis. Ablation of JGT mRNA levels by RNAi leads to the sequential reduction in base J and increased levels of hmU that dissipate rapidly. The analysis of JGT function confirms the two-step J synthesis model and demonstrates that JGT is the only glucosyltransferase enzyme required for the second step of the pathway. Similar to the activity of the related Ten-Eleven Translocation (TET) family of dioxygenases on 5mC, our studies also suggest the ability of the base J-binding protein enzymes to catalyze iterative oxidation of thymine in trypanosome DNA. Here we discuss the regulation of hmU and base J formation in the trypanosome genome by JGT and base J-binding protein.

Indexed as

DNA, ProtozoanEpigenesis, GeneticGene Knockout TechniquesGenome, ProtozoanGlucosidesGlucosyltransferasesMutagenesis, Site-DirectedPentoxylProtozoan ProteinsRNA InterferenceRNA, MessengerRNA, ProtozoanSubstrate SpecificityThymineTrypanosoma brucei bruceiUracil5-((glucopyranosyloxy)methyl)uracil5-hydroxymethyluracilDNA, ProtozoanGlucosidesGlucosyltransferasesPentoxylProtozoan ProteinsRNA, MessengerRNA, ProtozoanThymineUracilBase JDNA EnzymeEpigeneticsGlycosyltransferaseParasiteTranscription RegulationTrypanosoma bruceiTrypanosomatid

Identifiers

PMID24891501
PMCPMC4106341
OpenAlexW2117853570

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.