ArticleMolecular and cellular biology1998
Biosynthesis and function of the modified DNA base beta-D-glucosyl-hydroxymethyluracil in Trypanosoma brucei.
Article in Molecular and cellular biology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 71 citations in OpenAlex.
- G-Quadruplexes as Key Transcriptional Regulators in Neglected Trypanosomatid Parasites.Chembiochem : a European journal of chemical biology · 2023Review
- Advances in Protozoan Epigenetic Targets and Their Inhibitors for the Development of New Potential Drugs.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Behind Base J: The Roles of JBP1 and JBP2 on Trypanosomatids.Pathogens (Basel, Switzerland) · 2023Review
- Chromatin-Associated Protein Complexes Link DNA Base J and Transcription Termination inmSphere · 2021Article
- Emergence of a novel immune-evasion strategy from an ancestral protein fold in bacteriophage Mu.Nucleic acids research · 2020Article
- Identification of a novel base J binding protein complex involved in RNA polymerase II transcription termination in trypanosomes.PLoS genetics · 2020Article
- Article
- Genome-wide mapping of 5-hydroxymethyluracil in the eukaryote parasite Leishmania.Genome biology · 2017Article
- Base J glucosyltransferase does not regulate the sequence specificity of J synthesis in trypanosomatid telomeric DNA.Molecular and biochemical parasitology · 2015Article
- Defining the sequence requirements for the positioning of base J in DNA using SMRT sequencing.Nucleic acids research · 2015Article
- Glucosylated hydroxymethyluracil, DNA base J, prevents transcriptional readthrough in Leishmania.Cell · 2012Article
- Article
- Epigenetic regulation of transcription and virulence in Trypanosoma cruzi by O-linked thymine glucosylation of DNA.Molecular and cellular biology · 2011Article
- Identification, subcellular localization, biochemical properties, and high-resolution crystal structure of Trypanosoma brucei UDP-glucose pyrophosphorylase.Glycobiology · 2010Article
- JBP1 and JBP2 are two distinct thymidine hydroxylases involved in J biosynthesis in genomic DNA of African trypanosomes.Nucleic acids research · 2009Article
- Fe(II)/alpha-ketoglutarate hydroxylases involved in nucleobase, nucleoside, nucleotide, and chromatin metabolism.Dalton transactions (Cambridge, England : 2003) · 2008Article
- JBP2, a SWI2/SNF2-like protein, regulates de novo telomeric DNA glycosylation in bloodstream form Trypanosoma brucei.Molecular and biochemical parasitology · 2007Article
- Sugar nucleotide pools of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major.Eukaryotic cell · 2007Article
- Glycotargeting to improve cellular delivery efficiency of nucleic acids.Glycoconjugate journal · 2007Review
- Telomeric co-localization of the modified base J and contingency genes in the protozoan parasite Trypanosoma cruzi.Nucleic acids research · 2007Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
beta-D-Glucosyl-hydroxymethyluracil, also called J, is a modified DNA base conserved among kinetoplastid flagellates. In Trypanosoma brucei, the majority of J is present in repetitive DNA but the partial replacement of thymine by J also correlates with transcriptional repression of the variant surface glycoprotein (VSG) genes in the telomeric VSG gene expression sites. To gain a better understanding of the function of J, we studied its biosynthesis in T. brucei and found that it is made in two steps. In the first step, thymine in DNA is converted into hydroxymethyluracil by an enzyme that recognizes specific DNA sequences and/or structures. In the second step, hydroxymethyluracil is glucosylated by an enzyme that shows no obvious sequence specificity. We identified analogs of thymidine that affect the J content of the T. brucei genome upon incorporation into DNA. These analogs were used to study the function of J in the control of VSG gene expression sites. We found that incorporation of bromodeoxyuridine resulted in a 12-fold decrease in J content and caused a partial derepression of silent VSG gene expression site promoters, suggesting that J might strengthen transcriptional repression. Incorporation of hydroxymethyldeoxyuridine, resulting in a 15-fold increase in the J content, caused a reduction in the occurrence of chromosome breakage events sometimes associated with transcriptional switching between VSG gene expression sites in vitro. We speculate that these effects are mediated by the packaging of J-containing DNA into a condensed chromatin structure.
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