β-d-glucosyl-hydroxymethyluracil: A novel modified base present in the DNA of the parasitic protozoan T. brucei

@article{GommersAmpt1993dglucosylhydroxymethyluracilAN,
  title={$\beta$-d-glucosyl-hydroxymethyluracil: A novel modified base present in the DNA of the parasitic protozoan T. brucei},
  author={J H Gommers-Ampt and Fred van Leeuwen and Antonius L. J. de Beer and Johannes F. G. Vliegenthart and Miral Dizdaroglu and Jeffrey A. Kowalak and Pamela F. Crain and Piet Borst},
  journal={Cell},
  year={1993},
  volume={75},
  pages={1129-1136}
}
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162 Citations
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162 Citations

beta-D-glucosyl-hydroxymethyluracil, a novel base in African trypanosomes and other Kinetoplastida.
beta-D-glucosyl-hydroxymethyluracil is a conserved DNA modification in kinetoplastid protozoans and is abundant in their telomeres.
TLDR
The evolutionary conservation of J in kinetoplastid protozoans suggests that it has a general function, repression of transcription or recombination, or a combination of both.
Biosynthesis and Function of the Modified DNA Base β-d-Glucosyl-Hydroxymethyluracil inTrypanosoma brucei
TLDR
Study of J in T. brucei 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.
Quantitative Mass Spectrometry-Based Analysis of β-D-Glucosyl-5-Hydroxymethyluracil in Genomic DNA of Trypanosoma brucei
TLDR
Results provided direct evidence supporting that JBP proteins play an important role in oxidizing thymidine to form 5-HmdU, which facilitated the generation of dJ, the first report about the application of LC-MS/MS for the quantification of base J.
Identification of the Glucosyltransferase That Converts Hydroxymethyluracil to Base J in the Trypanosomatid Genome*
TLDR
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.
Site-specific Interactions of JBP with Base and Sugar Moieties in Duplex J-DNA
TLDR
Examination of molecular interactions that contribute to recognition of the glycosylated base in synthetic DNA substrates using modification interference, modification protection, DNA footprinting, and photocross-linking techniques finds that the two primary requirements for J-DNA recognition include contacts at base J and a base immediately 5′ of J (J-1).
Biosynthesis, and Possible Functions
TLDR
The identification and localization of base J in the genome of kinetoplastids, the enzymes involved in J biosynthesis, possible biological functions of J, and J as a potential target for chemotherapy of diseases caused by kinetiplastids are discussed.
The protein that binds to DNA base J in trypanosomatids has features of a thymidine hydroxylase
TLDR
Evidence is presented that a protein that binds to J in DNA, the J-binding protein 1 (JBP1), may also catalyze the first step in J biosynthesis, the conversion of thymine in DNA into hydroxymethyluracil and it is proposed that JBP1 is a thymidine hydroxylase responsible for the local amplification of J inserted by JBP2, another putative thymalid hydroxyase.
vidence that J-binding protein 2 is a thymidine hydroxylase catalyzing he first step in the biosynthesis of DNA base
TLDR
The genomic DNA of kinetoplastid parasites contains a unique modified base, -d-glucosylhydroxymethyluracil or base J, and two proteins, called JBP 1 and 2, display features of the family of Fe(II)–2-oxoglutarate dependent dioxygenases and are likely to be the enzymes catalyzing the first step in J biosynthesis.
Tandemly repeated DNA is a target for the partial replacement of thymine by beta-D-glucosyl-hydroxymethyluracil in Trypanosoma brucei.
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References

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The structure of V is determined and here the identity is presented, based on a detailed comparison of dV(p) with authentic HOMedU(p), showing: co-migration in three different liquid chromatography analyses, and identical UV absorbance characteristics.
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TLDR
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TLDR
At least some telomeric antigen-specific sequences of the procyclic trypanosomes (in vitro culture form) are not polymorphic, although they do not synthesize any variant-specific antigen mRNA; there is thus no absolute relationship between the absence of polymorphism and antigen gene transcription.
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