title: beta-D-glucosyl-hydroxymethyluracil is a conserved DNA modification in kinetoplastid protozoans and is abundant in their telomeres.
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.
authors.affiliation: Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: van Leeuwen
authors.forename: M C
authors.initials: MC
authors.lastname: Taylor
authors.forename: A
authors.initials: A
authors.lastname: Mondragon
authors.forename: H
authors.initials: H
authors.lastname: Moreau
authors.forename: W
authors.initials: W
authors.lastname: Gibson
authors.forename: R
authors.initials: R
authors.lastname: Kieft
authors.forename: P
authors.initials: P
authors.lastname: Borst
mesh_terms: D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D016054:DNA, Protozoan / Q000737:chemistry* / Q000235:genetics*; D056890:Eukaryota / Q000235:genetics*; D005960:Glucosides / Q000032:analysis*; D006801:Humans; D007313:Insecta / Q000469:parasitology; D007893:Leishmania donovani / Q000235:genetics; D008322:Mammals / Q000469:parasitology; D010802:Phylogeny; D012091:Repetitive Sequences, Nucleic Acid; D016615:Telomere / Q000235:genetics*; D014346:Trypanosoma brucei brucei / Q000235:genetics; D014349:Trypanosoma cruzi / Q000235:genetics; D014498:Uracil / Q000031:analogs & derivatives* / Q000032:analysis
chemical_list: D016054:DNA, Protozoan; D005960:Glucosides; C084880:5-((glucopyranosyloxy)methyl)uracil; D014498:Uracil