Base J: discovery, biosynthesis, and possible functions.
In 1993, a new base, beta-d-glucopyranosyloxymethyluracil (base J), was identified in the nuclear DNA of Trypanosoma brucei. Base J is the first hypermodified base found in eukaryotic DNA. It is present in all kinetoplastid flagellates analyzed and some unicellular flagellates closely related to trypanosomatids, but it has not been found in other protozoa or in metazoa. J is invariably present in the telomeric repeats of all organisms analyzed. Whereas in Leishmania nearly all J is telomeric, there are other repetitive DNA sequences containing J in T. brucei and T. cruzi, and most J is outside telomeres in Euglena. The biosynthesis of J occurs in two steps: First, a specific thymidine in DNA is converted into hydroxymethyldeoxyuridine (HOMedU), and then this HOMedU is glycosylated to form J. This review discusses 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 kinetoplastids.
Borst
Piet
P
Center of Biomedical Genetics, Division of Molecular Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands. p.borst@nki.nl
Sabatini
Robert
R
D000818:Animals; D001483:Base Sequence; D016054:DNA, Protozoan / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D055808:Drug Discovery; D044127:Epigenesis, Genetic; D005960:Glucosides / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007891:Leishmania / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D015800:Protozoan Proteins / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000378:metabolism; D014498:Uracil / Q000031:analogs & derivatives* / Q000096:biosynthesis
D016054:DNA, Protozoan; D004268:DNA-Binding Proteins; D005960:Glucosides; C505199:J-binding protein, Trypanosoma brucei; D015800:Protozoan Proteins; C084880:5-((glucopyranosyloxy)methyl)uracil; D014498:Uracil