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}
}
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.
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References

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TLDR
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.
Modification of telomeric DNA in Trypanosoma brucei; a role in antigenic variation?
TLDR
It is reported that PstI and PvuII restriction sites in silent telomeric antigen genes are partially uncleavable, presumably as a consequence of DNA modification.
A novel DNA nucleotide in Trypanosoma brucei only present in the mammalian phase of the life-cycle.
TLDR
It is concluded that pdJ is a novel eukaryotic DNA nucleotide and that it is probably responsible for the partial resistance to cleavage by PvuII and PstI of inactive telomeric VSG genes and may therefore be involved in the regulation of ES activity in bloodstream form trypanosomes.
Possible DNA modification in GC dinucleotides of Trypanosoma brucei telomeric sequences; relationship with antigen gene transcription
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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