Home LiteratureArticle Details
PMID: 9482891 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

beta-D-glucosyl-hydroxymethyluracil is a conserved DNA modification in kinetoplastid protozoans and is abundant in their telomeres.

van Leeuwen F, Taylor MC, Mondragon A, Moreau H, Gibson W, Kieft R, Borst P

Abstract

The unusual DNA base beta-D-glucosyl-hydroxymethyluracil, called "J, " replaces approximately 0.5-1% of Thy in DNA of African trypanosomes but has not been found in other organisms thus far. In Trypanosoma brucei, J is located predominantly in repetitive DNA, and its presence correlates with the silencing of telomeric genes. Using antibodies specific for J, we have developed sensitive assays to screen for J in a range of organisms and have found that J is not limited to trypanosomes that undergo antigenic variation but is conserved among Kinetoplastida. In all kinetoplastids tested, including the human pathogens Leishmania donovani and Trypanosoma cruzi, J was found to be abundantly present in the (GGGTTA)n telomere repeats. Outside Kinetoplastida, J was found only in Diplonema, a small phagotrophic marine flagellate, in which we also identified 5-MeCyt. Fractionation of Diplonema DNA showed that the two modifications are present in a common genome compartment, which suggests that they may have a similar function. Dinoflagellates appear to contain small amounts of modified bases that may be analogs of J. 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. T. brucei may have recruited J for the control of genes involved in antigenic variation.

MeSH Terms
Animals Base Sequence Conserved Sequence DNA, Protozoan/chemistry,genetics Eukaryota/genetics Glucosides/analysis Humans Insecta/parasitology Leishmania donovani/genetics Mammals/parasitology Phylogeny Repetitive Sequences, Nucleic Acid Telomere/genetics Trypanosoma brucei brucei/genetics Trypanosoma cruzi/genetics Uracil/analogs & derivatives,analysis
Chemicals
DNA, Protozoan Glucosides 5-((glucopyranosyloxy)methyl)uracil Uracil
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
van Leeuwen F
Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Taylor M C
Mondragon A
Moreau H
Gibson W
Kieft R
Borst P
References (36)
36 references, click to expand
  1. DNA methylation and genetic instability in colorectal cancer cells.
    Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2545-50 PMID: 9122232
  2. Cytosine methylation and the ecology of intragenomic parasites.
    Trends Genet. 1997 Aug;13(8):335-40 PMID: 9260521
  3. Chromosomal inheritance of epigenetic states in fission yeast during mitosis and meiosis.
    Cell. 1996 Jul 12;86(1):95-101 PMID: 8689692
  4. Ultrastructure of Diplonema ambulator larsen & patterson (euglenozoa) and its relationship to Isonema.
    Eur J Protistol. 1990 Jun 29;25(4):316-20 PMID: 23196044
  5. Transcriptional repression by methylation of CpG.
    J Cell Sci Suppl. 1992;16:9-14 PMID: 1297654
  6. Evolution of nuclear ribosomal RNAs in kinetoplastid protozoa: perspectives on the age and origins of parasitism.
    Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11608-12 PMID: 8265597
  7. A novel DNA nucleotide in Trypanosoma brucei only present in the mammalian phase of the life-cycle.
    Nucleic Acids Res. 1991 Apr 25;19(8):1745-51 PMID: 1674368
  8. Epigenetic phenomena in filamentous fungi: useful paradigms or repeat-induced confusion?
    Trends Genet. 1997 Aug;13(8):296-301 PMID: 9260514
  9. The base excision repair pathway.
    Trends Biochem Sci. 1995 Oct;20(10):391-7 PMID: 8533150
  10. Human telomeres are attached to the nuclear matrix.
    EMBO J. 1992 Feb;11(2):717-24 PMID: 1537344
  11. The bases of the nucleic acids of some bacterial and animal viruses: the occurrence of 5-hydroxymethylcytosine.
    Biochem J. 1953 Dec;55(5):774-82 PMID: 13115372
  12. 5-Hydroxymethyluracil-DNA glycosylase activity may be a differentiated mammalian function.
    Mutat Res. 1987 May;183(3):257-63 PMID: 3553917
  13. Methylation induced premeiotically in Ascobolus: coextension with DNA repeat lengths and effect on transcript elongation.
    Proc Natl Acad Sci U S A. 1993 May 15;90(10):4557-61 PMID: 8506299
  14. 5-Hydroxymethyluracil in the DNA of a dinoflagellate.
    Proc Natl Acad Sci U S A. 1973 Apr;70(4):1141-5 PMID: 4515611
  15. Early evolution and the origin of eukaryotes.
    Curr Opin Genet Dev. 1991 Dec;1(4):457-63 PMID: 1822277
  16. Ordered distribution of modified bases in the DNA of a dinoflagellate.
    Nucleic Acids Res. 1980 Oct 24;8(20):4709-25 PMID: 6255430
  17. Ancestral relationships of the major eukaryotic lineages.
    Microbiologia. 1996 Mar;12(1):17-28 PMID: 9019131
  18. How does DNA methylation repress transcription?
    Trends Genet. 1997 Nov;13(11):444-9 PMID: 9385841
  19. beta-D-glucosyl-hydroxymethyluracil: a novel modified base present in the DNA of the parasitic protozoan T. brucei.
    Cell. 1993 Dec 17;75(6):1129-36 PMID: 8261512
  20. The troublesome parasites--molecular and morphological evidence that Apicomplexa belong to the dinoflagellate-ciliate clade.
    Biosystems. 1991;25(1-2):75-83 PMID: 1649647
  21. Possible DNA modification in GC dinucleotides of Trypanosoma brucei telomeric sequences; relationship with antigen gene transcription.
    Nucleic Acids Res. 1984 Jul 11;12(13):5235-47 PMID: 6087278
  22. Molecular evolution of the 5'-terminal domain of large-subunit rRNA from lower eukaryotes. A broad phylogeny covering photosynthetic and non-photosynthetic protists.
    Biosystems. 1988;21(3-4):203-8 PMID: 3395679
  23. Silencing factors participate in DNA repair and recombination in Saccharomyces cerevisiae.
    Nature. 1997 Aug 28;388(6645):900-3 PMID: 9278054
  24. Modification of telomeric DNA in Trypanosoma brucei; a role in antigenic variation?
    Nucleic Acids Res. 1984 May 25;12(10):4153-70 PMID: 6328412
  25. Phylogenetic evidence of a role for 5-hydroxymethyluracil-DNA glycosylase in the maintenance of 5-methylcytosine in DNA.
    Nucleic Acids Res. 1989 Oct 11;17(19):7653-61 PMID: 2798122
  26. DNA repair.
    Curr Opin Cell Biol. 1993 Jun;5(3):424-33 PMID: 8352959
  27. Structure, subnuclear distribution, and nuclear matrix association of the mammalian telomeric complex.
    J Cell Biol. 1996 Nov;135(4):867-81 PMID: 8922373
  28. Hydroxymethyluracil in eukaryote DNA: a natural feature of the pyrrophyta (dinoflagellates).
    Science. 1976 Dec 3;194(4269):1062-4 PMID: 988637
  29. Ribosomal RNA sequences of Sarcocystis muris, Theileria annulata and Crypthecodinium cohnii reveal evolutionary relationships among apicomplexans, dinoflagellates, and ciliates.
    Mol Biochem Parasitol. 1991 Mar;45(1):147-54 PMID: 1904987
  30. DNA methylation inhibits elongation but not initiation of transcription in Neurospora crassa.
    Genes Dev. 1997 Sep 15;11(18):2383-95 PMID: 9308966
  31. Ancient origin of RNA editing in kinetoplastid protozoa.
    Curr Opin Genet Dev. 1994 Dec;4(6):887-94 PMID: 7888760
  32. The telomeric GGGTTA repeats of Trypanosoma brucei contain the hypermodified base J in both strands.
    Nucleic Acids Res. 1996 Jul 1;24(13):2476-82 PMID: 8692684
  33. A high level of thymine replacement by 5-hydroxymethyluracil in nuclear DNA of the primitive dinoflagellate Prorocentrum micans E.
    Eur J Cell Biol. 1982 Jun;27(2):151-5 PMID: 6889504
  34. Control of antigenic variation in African trypanosomes.
    Cold Spring Harb Symp Quant Biol. 1993;58:105-14 PMID: 7956020
  35. MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin.
    Cell. 1997 Feb 21;88(4):471-81 PMID: 9038338
  36. Localization of the modified base J in telomeric VSG gene expression sites of Trypanosoma brucei.
    Genes Dev. 1997 Dec 1;11(23):3232-41 PMID: 9389654
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1998-03-03
Pages
2366-71
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC19348
Subset
IM
Corrections
CommentIn
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]