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

Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2366-71. doi: 10.1073/pnas.95.5.2366.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Conserved Sequence
  • DNA, Protozoan / chemistry*
  • DNA, Protozoan / 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*
  • Uracil / analysis

Substances

  • DNA, Protozoan
  • Glucosides
  • 5-((glucopyranosyloxy)methyl)uracil
  • Uracil